{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:17:44Z","timestamp":1790072264232,"version":"4.0.1"},"reference-count":270,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes.<\/jats:p>","DOI":"10.3390\/molecules22071037","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T08:16:18Z","timestamp":1498205778000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":196,"title":["An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs"],"prefix":"10.3390","volume":"22","author":[{"given":"Ver\u00f3nica","family":"Ruiz-Torres","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-3863","authenticated-orcid":false,"given":"Jose","family":"Encinar","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-7978","authenticated-orcid":false,"given":"Mar\u00eda","family":"Herranz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-9953","authenticated-orcid":false,"given":"Vicente","family":"Galiano","sequence":"additional","affiliation":[{"name":"Physics and Computer Architecture Department, Miguel Hern\u00e1ndez University, Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-0795","authenticated-orcid":false,"given":"Enrique","family":"Barraj\u00f3n-Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Micol","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology (IBMC), Miguel Hern\u00e1ndez University (UMH), Avda. Universidad s\/n, Elche 03202, Spain"},{"name":"CIBER, Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n, CIBERobn, Instituto de Salud Carlos III., Palma de Mallorca 07122, Spain (CB12\/03\/30038)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2016). Cancer Facts & Figures 2016, American Cancer Society."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/j.drudis.2016.06.032","article-title":"Cancer control potential of marine natural product scaffolds through inhibition of tumor cell migration and invasion","volume":"21","author":"Mudit","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","first-page":"739","article-title":"FDA approves first immunotherapy combo","volume":"14","author":"Mullard","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.2174\/1389450117666160201114752","article-title":"Immunotherapy and hormone-therapy in metastatic breast cancer: A review and an update","volume":"17","author":"Nicolini","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/ijc.30006","article-title":"Single-cell profiling approaches to probing tumor heterogeneity","volume":"139","author":"Khoo","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrg1748","article-title":"The epigenetic progenitor origin of human cancer","volume":"7","author":"Feinberg","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1126\/science.1116364","article-title":"The renaissance of natural products as drug candidates","volume":"310","author":"Paterson","year":"2005","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cell.2008.04.019","article-title":"Xenohormesis: Sensing the chemical cues of other species","volume":"133","author":"Howitz","year":"2008","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1021\/np068054v","article-title":"Natural products as sources of new drugs over the last 25 years","volume":"70","author":"Newman","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for emerging pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1021\/cr900019j","article-title":"Impact of natural products on developing new anti-cancer agents","volume":"109","author":"Cragg","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1039\/np9971400453","article-title":"Secondary metabolites from marine microorganisms: Bacteria, protozoa, algae and fungi. Achievements and prospects","volume":"14","author":"Pietra","year":"1997","journal-title":"Nat. Prod. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/BF00396537","article-title":"Microbial production of primary metabolites","volume":"67","author":"Demain","year":"1980","journal-title":"Naturwissenschaften"},{"key":"ref_15","first-page":"126","article-title":"Role of secondary metabolites in chemical defence mechanisms in plants","volume":"154","author":"Harborne","year":"1990","journal-title":"Ciba Found. Symp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3354\/dao02560","article-title":"Screening bacterial metabolites for inhibitory effects against batrachochytrium dendrobatidis using a spectrophotometric assay","volume":"103","author":"Bell","year":"2013","journal-title":"Dis. Aquat. Org."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Elufioye, T.O., and Badal, S. (2017). Chapter 1\u2014Background to pharmacognosy. Pharmacognosy, Academic Press.","DOI":"10.1016\/B978-0-12-802104-0.00001-9"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nrd2487","article-title":"Drug development from marine natural products","volume":"8","author":"Molinski","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8114","DOI":"10.1128\/JVI.00287-15","article-title":"Marine snails and slugs: A great place to look for antiviral drugs","volume":"89","author":"Dang","year":"2015","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10126-008-9118-5","article-title":"A fatty acid from the diatom phaeodactylum tricornutum is antibacterial against diverse bacteria including multi-resistant Staphylococcus aureus (MRSA)","volume":"11","author":"Desbois","year":"2009","journal-title":"Mar. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/jo802232u","article-title":"Celebesides A-C and theopapuamides B-D, depsipeptides from an Indonesian sponge that inhibit HIV-1 entry","volume":"74","author":"Plaza","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1016\/j.bmcl.2010.07.084","article-title":"Neopetrosiamine A, biologically active bis-piperidine alkaloid from the caribbean sea sponge neopetrosia proxima","volume":"20","author":"Wei","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1097\/00001813-200011000-00003","article-title":"Pharmaceutical development of anticancer agents derived from marine sources","volume":"11","author":"Nuijen","year":"2000","journal-title":"Anticancer Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/np800617a","article-title":"Arenamides A-C, cytotoxic NFkappaB inhibitors from the marine actinomycete Salinispora arenicola","volume":"72","author":"Asolkar","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.procbio.2015.07.018","article-title":"Stalked sea squirt (Styela clava) tunic waste as a valuable bioresource: Cosmetic and antioxidant activities","volume":"50","author":"Lee","year":"2015","journal-title":"Process Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1016\/S1473-3099(16)30323-1","article-title":"Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections","volume":"17","author":"Abdelmohsen","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.drudis.2010.09.002","article-title":"Marine natural products as sources of novel scaffolds: Achievement and concern","volume":"15","author":"Kong","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0168-1656(99)00053-X","article-title":"The bioprocess\u2014Technological potential of the sea","volume":"70","author":"Pomponi","year":"1999","journal-title":"J. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.tibtech.2008.10.005","article-title":"Panning for chemical gold: Marine bacteria as a source of new therapeutics","volume":"27","author":"Williams","year":"2009","journal-title":"Trends Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/md201014","article-title":"New marine derived anticancer therapeutics\u2014A journey from the sea to clinical trials","volume":"2","author":"Jimeno","year":"2004","journal-title":"Mar. Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"572859","DOI":"10.1155\/2013\/572859","article-title":"Marine invertebrate natural products for anti-inflammatory and chronic diseases","volume":"2013","author":"Senthilkumar","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/B978-0-12-416003-3.00024-X","article-title":"Chapter 24\u2014Bioactive secondary metabolites from marine microbes for drug discovery","volume":"Volume 65","year":"2012","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1039\/C4NP00144C","article-title":"Marine natural products","volume":"32","author":"Blunt","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-416003-3.00001-9","article-title":"Chapter 1\u2014Medicinal foods from marine animals: Current status and prospects","volume":"Volume 65","year":"2012","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/nt.2620020507","article-title":"Kainic acid and 1\u2032-hydroxykainic acid from palmariales","volume":"2","author":"Ramsey","year":"1994","journal-title":"Nat. Toxins"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1021\/jo01063a066","article-title":"Contributions to the study of marine products. L. Phospholipids of sponges1,2","volume":"26","author":"Landowne","year":"1961","journal-title":"J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tips.2010.02.005","article-title":"The odyssey of marine pharmaceuticals: A current pipeline perspective","volume":"31","author":"Mayer","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1021\/bi00382a004","article-title":"Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom","volume":"26","author":"Olivera","year":"1987","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/bjc.2014.149","article-title":"Trabectedin, a drug acting on both cancer cells and the tumour microenvironment","volume":"111","author":"Badri","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1158\/1535-7163.MCT-04-0345","article-title":"The primary antimitotic mechanism of action of the synthetic halichondrin e7389 is suppression of microtubule growth","volume":"4","author":"Jordan","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/phar.1170","article-title":"Brentuximab vedotin: A CD30-directed antibody-cytotoxic drug conjugate","volume":"33","author":"Newland","year":"2013","journal-title":"Pharmacotherapy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/B978-0-12-416003-3.00009-3","article-title":"Medicinal benefits of marine invertebrates: Sources for discovering natural drug candidates","volume":"65","year":"2012","journal-title":"Adv. Food Nutr. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1023\/A:1003987117508","article-title":"Exploited marine invertebrates: Genetics and fisheries","volume":"420","author":"Thorpe","year":"2000","journal-title":"Hydrobiologia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.chembiol.2011.12.014","article-title":"Lessons from the past and charting the future of marine natural products drug discovery and chemical biology","volume":"19","author":"Gerwick","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.steroids.2015.06.012","article-title":"Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4\/Cyclin D1","volume":"102","author":"Saikia","year":"2015","journal-title":"Steroids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3390\/md9040514","article-title":"Statistical research on marine natural products based on data obtained between 1985 and 2008","volume":"9","author":"Hu","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9842","DOI":"10.3390\/molecules17089842","article-title":"Bioprospecting of marine invertebrates for new natural products\u2014A chemical and zoogeographical perspective","volume":"17","author":"Leal","year":"2012","journal-title":"Molecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1163\/18759866-07602004","article-title":"Marine invertebrate diversity in Aristotle\u2019s zoology","volume":"76","author":"Voultsiadou","year":"2007","journal-title":"Contrib. Zool."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S1359-6446(03)02713-2","article-title":"Drugs from the deep: Marine natural products as drug candidates","volume":"8","author":"Haefner","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.3390\/md11072510","article-title":"Marine pharmacology in 2009\u20132011: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action","volume":"11","author":"Mayer","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_51","unstructured":"Delgoda, R. (2017). Chapter 9\u2014Alkaloids A2\u2014Badal, Simone. Pharmacognosy, Academic Press."},{"key":"ref_52","first-page":"963","article-title":"Alkaloids produced by endophytic fungi: A review","volume":"7","author":"Zhang","year":"2012","journal-title":"Nat. Prod. Commun."},{"key":"ref_53","first-page":"1","article-title":"Introduction to the analysis of bioactive compounds in marine samples","volume":"Volume 65","author":"Duarte","year":"2014","journal-title":"Comprehensive Analytical Chemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1021\/cr00021a009","article-title":"Marine pyridoacridine alkaloids: Structure, synthesis, and biological chemistry","volume":"93","author":"Molinski","year":"1993","journal-title":"Chem. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.bmc.2009.12.028","article-title":"From anti-fouling to biofilm inhibition: New cytotoxic secondary metabolites from two Indonesian Agelas sponges","volume":"18","author":"Hertiani","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1021\/np050424c","article-title":"(+)-Agelasine D: Improved synthesis and evaluation of antibacterial and cytotoxic activities","volume":"69","author":"Vik","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fitote.2016.09.009","article-title":"Ancistectorine D, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8\u2032- and 7,1\u2032-linked metabolites from the Chinese liana Ancistrocladus tectorius","volume":"115","author":"Bringmann","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1021\/np800212g","article-title":"Agelasines J, K, and L from the Solomon Islands marine sponge Agelas cf. mauritiana","volume":"71","author":"Appenzeller","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.cclet.2017.01.009","article-title":"Three new non-brominated pyrrole alkaloids from the South China Sea sponge Agelas nakamurai","volume":"28","author":"Chu","year":"2017","journal-title":"Chin. Chem. Lett."},{"key":"ref_60","first-page":"4624","article-title":"Complex enzymes in microbial natural product biosynthesis, part B: Polyketides, aminocoumarins and carbohydrates. Preface","volume":"459","author":"Hopwood","year":"2009","journal-title":"Methods Enzymol"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/j.phytochem.2009.04.010","article-title":"Polyketide synthases of bacterial symbionts in sponges\u2014Evolution-based applications in natural products research","volume":"70","author":"Hochmuth","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1021\/np200108h","article-title":"Chemical constituents of a marine fungus, Arthrinium sacchari","volume":"74","author":"Tsukada","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.3390\/md8082340","article-title":"Terpenes from marine-derived fungi","volume":"8","author":"Ebel","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jff.2010.01.003","article-title":"Development and biological activities of marine-derived bioactive peptides: A review","volume":"2","author":"Kim","year":"2010","journal-title":"J. Funct. Foods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.3390\/md13074006","article-title":"Marine peptides: Bioactivities and applications","volume":"13","author":"Cheung","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3389\/fphar.2016.00333","article-title":"The pharmacological potential of non-ribosomal peptides from marine sponge and tunicates","volume":"7","author":"Agrawal","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.3390\/md12084539","article-title":"Marine sponge derived natural products between 2001 and 2010: Trends and opportunities for discovery of bioactives","volume":"12","author":"Mehbub","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.3390\/ijms16036018","article-title":"The effects of marine carbohydrates and glycosylated compounds on human health","volume":"16","author":"Kang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.3390\/md8092435","article-title":"Marine polysaccharides in pharmaceutical applications: An overview","volume":"8","author":"Laurienzo","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ijbiomac.2016.06.100","article-title":"Bioactivities, isolation and purification methods of polysaccharides from natural products: A review","volume":"92","author":"Shi","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1128\/IAI.00472-08","article-title":"Identification of the smallest structure capable of evoking opsonophagocytic antibodies against Streptococcus pneumoniae type 14","volume":"76","author":"Safari","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.micres.2014.01.001","article-title":"Synergistic combination of marine oligosaccharides and azithromycin against Pseudomonas aeruginosa","volume":"169","author":"He","year":"2014","journal-title":"Microbiol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.2174\/0929867013372193","article-title":"Glycosides in medicine: \u201cThe role of glycosidic residue in biological activity\u201d","volume":"8","author":"Kren","year":"2001","journal-title":"Curr. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1747-0285.2008.00741.x","article-title":"The structure of glycosaminoglycans and their interactions with proteins","volume":"72","author":"Gandhi","year":"2008","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s00018-004-4293-7","article-title":"Heparan sulfate-protein interactions: Therapeutic potential through structure-function insights","volume":"62","author":"Coombe","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_76","first-page":"536","article-title":"The mechanism of action of plitidepsin","volume":"10","author":"Martinez","year":"2009","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/bju.12437","article-title":"Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and\/or metastasized urothelial cancer: SUSE (AUO-AB 31\/05)","volume":"113","author":"Krege","year":"2014","journal-title":"BJU Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1200\/JCO.2013.52.5683","article-title":"Phase I\/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer","volume":"32","author":"Bendell","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Molina-Guijarro, J.M., Garc\u00eda, C., Mac\u00edas, \u00c1., Garc\u00eda-Fern\u00e1ndez, L.F., Moreno, C., Reyes, F., Mart\u00ednez-Leal, J.F., Fern\u00e1ndez, R., Mart\u00ednez, V., and Valenzuela, C. (2015). Elisidepsin interacts directly with glycosylceramides in the plasma membrane of tumor cells to induce necrotic cell death. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140782"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1365-2958.2009.06665.x","article-title":"A genetic approach for finding small rnas regulators of genes of interest identifies RybC as regulating the DpiA\/DpiB two-component system","volume":"72","author":"Mandin","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1073\/pnas.83.17.6238","article-title":"The pseudopterosins: Anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae","volume":"83","author":"Look","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s00706-012-0920-4","article-title":"An improved and efficient synthesis for IPL576,092 and its analogues","volume":"144","author":"Liu","year":"2013","journal-title":"Monatshefte Chem. Chem. Mon."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12328","DOI":"10.3390\/molecules190812328","article-title":"PM00104 (Zalypsis\u00ae): A marine derived alkylating agent","volume":"19","author":"Petek","year":"2014","journal-title":"Molecules"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.3390\/md8102702","article-title":"Marine antitumor drugs: Status, shortfalls and strategies","volume":"8","author":"Bhatnagar","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12442","DOI":"10.1038\/srep12442","article-title":"Bryostatin activates HIV-1 latent expression in human astrocytes through a PKC and NF-kB-dependent mechanism","volume":"5","author":"Diaz","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1182\/blood.V128.22.1856.1856","article-title":"Polatuzumab vedotin combined with obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (G-CHP) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL): Preliminary results of a phase Ib\/II dose-escalation study","volume":"128","author":"Kolibaba","year":"2016","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1182\/blood-2006-12-062877","article-title":"Clinical efficacy of zanolimumab (HuMax-CD4): Two phase 2 studies in refractory cutaneous T-cell lymphoma","volume":"109","author":"Kim","year":"2007","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3390\/md12010255","article-title":"Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development","volume":"12","author":"Newman","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14328","DOI":"10.1523\/JNEUROSCI.1010-14.2014","article-title":"Hydroxamic acid-based histone deacetylase (HDAC) inhibitors can mediate neuroprotection independent of hdac inhibition","volume":"34","author":"Sleiman","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.toxlet.2013.06.213","article-title":"A diverse induction of apoptosis by trabectedin in MCF-7 (HER2\u2212\/ER+) and MDA-MB-453 (HER2+\/ER\u2212) breast cancer cells","volume":"221","author":"Atmaca","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7305","DOI":"10.1016\/S0040-4020(00)00629-3","article-title":"A new antitumor isoquinoline alkaloid from the marine nudibranch Jorunna funebris","volume":"56","author":"Fontana","year":"2000","journal-title":"Tetrahedron"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1021\/np030092g","article-title":"Renieramycin J, a highly cytotoxic tetrahydroisoquinoline alkaloid, from a marine sponge Neopetrosia sp.","volume":"66","author":"Oku","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/0975-7406.171700","article-title":"Exploring the ocean for new drug developments: Marine pharmacology","volume":"8","author":"Malve","year":"2016","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.clinthera.2012.06.003","article-title":"Eribulin mesylate (E7389): Review of efficacy and tolerability in breast, pancreatic, head and neck, and non\u2013small cell lung cancer","volume":"34","author":"Scarpace","year":"2012","journal-title":"Clin. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2174\/138955708783744137","article-title":"The structure activity relationship of discodermolide analogues","volume":"8","author":"Shaw","year":"2008","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_96","first-page":"38","article-title":"A phase II trial of bryostatin 1 in the treatment of metastatic colorectal cancer","volume":"7","author":"Zonder","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Caplan, S.L., Zheng, B., Dawson-Scully, K., White, C.A., and West, L.M. (2016). Pseudopterosin A: Protection of synaptic function and potential as a neuromodulatory agent. Mar. Drugs, 14.","DOI":"10.3390\/md14030055"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"L401","DOI":"10.1016\/S0024-3205(98)00229-X","article-title":"Pharmacological characterization of the pseudopterosins: Novel anti-inflammatory natural products isolated from the caribbean soft coral, Pseudopterogorgia elisabethae","volume":"62","author":"Mayer","year":"1998","journal-title":"Life Sci."},{"key":"ref_99","first-page":"31173","article-title":"Conus Peptides: Biodiversity-based discovery and exogenomics","volume":"281","author":"Olivera","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1182\/blood-2014-08-595801","article-title":"Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory hodgkin lymphoma","volume":"125","author":"Gopal","year":"2015","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.lungcan.2006.10.002","article-title":"A phase 2 study of TZT-1027, administered weekly to patients with advanced non-small cell lung cancer following treatment with platinum-based chemotherapy","volume":"55","author":"Riely","year":"2007","journal-title":"Lung Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/bjc.1998.570","article-title":"In vitro activity of aplidine, a new marine-derived anti-cancer compound, on freshly explanted clonogenic human tumour cells and haematopoietic precursor cells","volume":"78","author":"Depenbrock","year":"1998","journal-title":"Br. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1124\/jpet.107.132662","article-title":"Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via Rac1\/c-JUN NH2-terminal kinase activation in human melanoma cells","volume":"324","author":"Zarich","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1158\/0008-5472.CAN-07-5725","article-title":"Aplidin, a marine organism-derived compound with potent antimyeloma activity in vitro and in vivo","volume":"68","author":"Mitsiades","year":"2008","journal-title":"Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1007\/s10637-011-9740-3","article-title":"The cytotoxic activity of Aplidin in chronic lymphocytic leukemia (CLL) is mediated by a direct effect on leukemic cells and an indirect effect on monocyte-derived cells","volume":"30","author":"Morande","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/j.1349-7006.2007.00418.x","article-title":"Tumor-specific antivascular effect of TZT-1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy","volume":"98","author":"Natsume","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1158\/1078-0432.CCR-06-0179","article-title":"Phase I and pharmacokinetic study of tasidotin hydrochloride (ILX651), a third-generation dolastatin-15 analogue, administered weekly for 3 weeks every 28 days in patients with advanced solid tumors","volume":"12","author":"Mita","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6594","DOI":"10.1021\/jo960877+","article-title":"Kahalalides: Bioactive peptides from a marine mollusk Elysia rufescens and its algal diet Bryopsis sp.","volume":"61","author":"Hamann","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1147P","DOI":"10.1093\/annonc\/mdw379.42","article-title":"A phase 2 study of glembatumumab vedotin (GV), an antibody-drug conjugate (ADC) targeting gpNMB, in advanced melanoma","volume":"27","author":"Ott","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_110","first-page":"1078-0432","article-title":"Phase I study of the anti-CD22 antibody-drug conjugate pinatuzumab vedotin with\/without rituximab in patients with relapsed\/refractory B-cell non-Hodgkin\u2019s lymphoma","volume":"6","author":"Advani","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.coi.2016.02.008","article-title":"New developments for antibody-drug conjugate-based therapeutic approaches","volume":"40","author":"Lambert","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1016\/j.bmcl.2004.08.024","article-title":"Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: Modification of the a segment","volume":"14","author":"Yamashita","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s002800050564","article-title":"Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation","volume":"39","author":"Anderson","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejps.2016.05.032","article-title":"A novel hybrid drug between two potent anti-tubulin agents as a potential prolonged anticancer approach","volume":"91","author":"Marchetti","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jcis.2016.10.041","article-title":"Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy","volume":"487","author":"Liu","year":"2017","journal-title":"J. Colloid Interface Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/bjc.2014.49","article-title":"Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1","volume":"110","author":"Akashi","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1039\/C5TB02598B","article-title":"Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells","volume":"4","author":"Kuo","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6663","DOI":"10.1158\/1078-0432.CCR-08-0376","article-title":"Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors","volume":"14","author":"Kristeleit","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The clonal evolution of tumor cell populations","volume":"194","author":"Nowell","year":"1976","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_122","first-page":"309","article-title":"Tubulin and microtubules as targets for anticancer drugs","volume":"5","author":"Hadfield","year":"2003","journal-title":"Prog. Cell Cycle Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Avenda\u00f1o, C., and Men\u00e9ndez, J.C. (2015). Chapter 9\u2014Anticancer drugs targeting tubulin and microtubules. Medicinal Chemistry of Anticancer Drugs, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-444-62649-3.00009-0"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S1471-4892(01)00064-9","article-title":"Past and future of the mitotic spindle as an oncology target","volume":"1","author":"Wood","year":"2001","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ejmech.2014.09.051","article-title":"Recent developments in tubulin polymerization inhibitors: An overview","volume":"87","author":"Kaur","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1158\/1535-7163.MCT-13-0791","article-title":"Targeting microtubules by natural agents for cancer therapy","volume":"13","author":"Mukhtar","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1568011023354290","article-title":"Mechanism of action of antitumor drugs that interact with microtubules and tubulin","volume":"2","author":"Jordan","year":"2002","journal-title":"Curr. Med. Chem. Anticancer Agents"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1021\/np010049y","article-title":"Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1","volume":"64","author":"Luesch","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/0006-2952(90)90613-P","article-title":"Dolastatin 10, a powerful cytostatic peptide derived from a marine animal","volume":"39","author":"Bai","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0006-2952(01)00898-X","article-title":"Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10","volume":"63","author":"Edler","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1039\/b705663j","article-title":"The synthetic challenge of diazonamide a, a macrocyclic indole bis-oxazole marine natural product","volume":"25","author":"Lachia","year":"2008","journal-title":"Nat. Prod. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1124\/mol.63.6.1273","article-title":"Diazonamide a and a synthetic structural analog: Disruptive effects on mitosis and cellular microtubules and analysis of their interactions with tubulin","volume":"63","author":"Vervoort","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1002\/anie.200702243","article-title":"Total synthesis of the originally proposed and revised structures of palmerolide A","volume":"46","author":"Nicolaou","year":"2007","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jsbi.2001.4359","article-title":"Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin","volume":"135","author":"Llorca","year":"2001","journal-title":"J. Struct. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2174\/1381612013397492","article-title":"Spongistatins as tubulin targeting agents","volume":"7","author":"Uckun","year":"2001","journal-title":"Curr. Pharm. Des."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"17667","DOI":"10.1021\/ja053663v","article-title":"Hybrids of the hemiasterlin analogue taltobulin and the dolastatins are potent antimicrotubule agents","volume":"127","author":"Zask","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10637-010-9398-2","article-title":"Peloruside A inhibits microtubule dynamics in a breast cancer cell line MCF7","volume":"29","author":"Chan","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1039\/C4NP00024B","article-title":"Zampanolide and dactylolide: Cytotoxic tubulin-assembly agents and promising anticancer leads","volume":"31","author":"Chen","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1021\/jm901249g","article-title":"Microtubule-stabilizing activity of zampanolide, a potent macrolide isolated from the tongan marine sponge Cacospongia mycofijiensis","volume":"52","author":"Field","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.chembiol.2012.05.008","article-title":"Zampanolide, a potent new microtubule stabilizing agent, covalently reacts with the taxane luminal site in both tubulin \u03b1,\u03b2-heterodimers and microtubules","volume":"19","author":"Field","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-2952(03)00192-8","article-title":"Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin","volume":"66","author":"Isbrucker","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Paterson, I., Britton, R., Delgado, O., and Wright, A.E. (2004). Stereochemical determination of dictyostatin, a novel microtubule-stabilising macrolide from the marine sponge Corallistidae sp.. Chem. Commun. (Camb.), 632\u2013633.","DOI":"10.1002\/chin.200431189"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"15053","DOI":"10.1021\/bi050685l","article-title":"Tubulin assembly, taxoid site binding, and cellular effects of the microtubule-stabilizing agent dictyostatin","volume":"44","author":"Madiraju","year":"2005","journal-title":"Biochemistry"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1158\/1535-7163.MCT-10-1048","article-title":"A simplified synthesis of novel dictyostatin analogues with in vitro activity against epothilone b-resistant cells and antiangiogenic activity in zebrafish embryos","volume":"10","author":"Vollmer","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1021\/ml400233e","article-title":"Mt-stabilizer, dictyostatin, exhibits prolonged brain retention and activity: Potential therapeutic implications","volume":"4","author":"Brunden","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/cbdd.12475","article-title":"The unique binding mode of laulimalide to two tubulin protofilaments","volume":"86","author":"Churchill","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1136\/pgmj.2008.072629","article-title":"Programmed cell death and cancer","volume":"85","author":"Sun","year":"2009","journal-title":"Postgrad. Med. J."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-015-0321-5","article-title":"Apoptosis, autophagy, necroptosis, and cancer metastasis","volume":"14","author":"Su","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4161\/auto.1.2.1738","article-title":"Does autophagy contribute to cell death?","volume":"1","author":"Debnath","year":"2005","journal-title":"Autophagy"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.biocel.2009.06.010","article-title":"Apoptosis signaling in cancer stem cells","volume":"42","author":"Fulda","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0006-291X(03)00614-4","article-title":"Mitochondrial control of apoptosis: An introduction","volume":"304","author":"Kroemer","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.drup.2005.05.001","article-title":"The role of caspases in cell death and differentiation","volume":"8","author":"Oliver","year":"2005","journal-title":"Drug Resist. Updat."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrc883","article-title":"The Bcl2 family: Regulators of the cellular life-or-death switch","volume":"2","author":"Cory","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/nrc2254","article-title":"Role of autophagy in cancer","volume":"7","author":"Mathew","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.2174\/138945012804545489","article-title":"Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents","volume":"13","author":"Mukhtar","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1016\/j.cellsig.2014.08.019","article-title":"The role of PI3K\/AKT\/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration","volume":"26","year":"2014","journal-title":"Cell Signal."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1128\/CDLI.7.6.947-952.2000","article-title":"Jasplakinolide induces apoptosis in various transformed cell lines by a caspase-3-like protease-dependent pathway","volume":"7","author":"Odaka","year":"2000","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3390\/md7030435","article-title":"Two new jaspamide derivatives from the marine sponge Jaspis splendens","volume":"7","author":"Ebada","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1021\/jm9013554","article-title":"New structures and bioactivity properties of jasplakinolide (jaspamide) analogues from marine sponges","volume":"53","author":"Robinson","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s002800050475","article-title":"Antitumour evaluation of dolastatins 10 and 15 and their measurement in plasma by radioimmunoassay","volume":"38","author":"Aherne","year":"1996","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/00001813-199506000-00005","article-title":"The bcl-2 and p53 oncoproteins can be modulated by bryostatin 1 and dolastatins in human diffuse large cell lymphoma","volume":"6","author":"Maki","year":"1995","journal-title":"Anticancer Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.clcc.2012.01.002","article-title":"A novel polypeptide extracted from ciona savignyi induces apoptosis through a mitochondrial-mediated pathway in human colorectal carcinoma cells","volume":"11","author":"Cheng","year":"2012","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1258\/ebm.2012.011337","article-title":"A novel polypeptide from meretrix meretrix linnaeus inhibits the growth of human lung adenocarcinoma","volume":"237","author":"Wang","year":"2012","journal-title":"Exp. Biol. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nchembio.1797","article-title":"Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B","volume":"11","author":"Potts","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1021\/ol101716x","article-title":"Monanchocidin: A new apoptosis-inducing polycyclic guanidine alkaloid from the marine sponge Monanchora pulchra","volume":"12","author":"Guzii","year":"2010","journal-title":"Org. Lett."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"17328","DOI":"10.18632\/oncotarget.4175","article-title":"Marine alkaloid monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization","volume":"6","author":"Dyshlovoy","year":"2015","journal-title":"Oncotarget"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"879585","DOI":"10.1093\/ecam\/nep042","article-title":"Bioactivity of the Murex Homeopathic Remedy and of Extracts from an Australian Muricid Mollusc against Human Cancer Cells","volume":"2011","author":"Benkendorff","year":"2011","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.bmc.2006.10.035","article-title":"In vitro cytotoxicity evaluation of some substituted isatin derivatives","volume":"15","author":"Vine","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4161\/cbt.9.5.10887","article-title":"Enhanced acute apoptotic response to azoxymethane-induced DNA damage in the rodent colonic epithelium by tyrian purple precursors: A potential colorectal cancer chemopreventative","volume":"9","author":"Westley","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3390\/md10010064","article-title":"Marine compounds selectively induce apoptosis in female reproductive cancer cells but not in primary-derived human reproductive granulosa cells","volume":"10","author":"Edwards","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1021\/np010053+","article-title":"Makaluvamine P, a new cytotoxic pyrroloiminoquinone from Zyzzya cf. fuliginosa","volume":"64","author":"Casapullo","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1016\/j.bmcl.2007.02.065","article-title":"Analogs of the marine alkaloid makaluvamines: Synthesis, topoisomerase II inhibition, and anticancer activity","volume":"17","author":"Shinkre","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Chen, T., Xu, Y., Guo, H., Liu, Y., Hu, P., Yang, X., Li, X., Ge, S., Velu, S.E., and Nadkarni, D.H. (2011). Experimental therapy of ovarian cancer with synthetic makaluvamine analog: In vitro and in vivo anticancer activity and molecular mechanisms of action. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020729"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1039\/C4MD00286E","article-title":"Analogues of the marine alkaloids oroidin, clathrodin, and hymenidin induce apoptosis in human HepG2 and THP-1 cancer cells","volume":"6","author":"Tomasic","year":"2015","journal-title":"MedChemComm"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/jsfa.4678","article-title":"In vitro and in vivo anti-tumour activities of echinoside A and ds-echinoside A from Pearsonothuria graeffei","volume":"92","author":"Zhao","year":"2012","journal-title":"J. Sci. Food Agric."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"27071","DOI":"10.1038\/srep27071","article-title":"Stellettin B induces G1 arrest, apoptosis and autophagy in human non-small cell lung cancer A549 cells via blocking PI3K\/Akt\/mTOR pathway","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1139\/v90-003","article-title":"Frondoside A. A novel triterpene glycoside from the holothurian Cucumariafrondosa","volume":"68","author":"Girard","year":"1990","journal-title":"Can. J. Chem."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1002\/ijc.29977","article-title":"The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer","volume":"138","author":"Dyshlovoy","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.fct.2014.06.001","article-title":"Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK\/p38 MAPK\u2013CHOP signaling pathways","volume":"71","author":"Do","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"34085","DOI":"10.1074\/jbc.M705593200","article-title":"Requirement of phospholipase D for ilimaquinone-induced Golgi membrane fragmentation","volume":"282","author":"Sonoda","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1021\/np400320r","article-title":"Inducers of hypoxic response: Marine sesquiterpene quinones activate HIF-1","volume":"76","author":"Du","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/pcan.2013.38","article-title":"Tanshinone IIA inhibits human prostate cancer cells growth by induction of endoplasmic reticulum stress in vitro and in vivo","volume":"16","author":"Chiu","year":"2013","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3390\/md13010543","article-title":"Activation of p53 with ilimaquinone and ethylsmenoquinone, marine sponge metabolites, induces apoptosis and autophagy in colon cancer cells","volume":"13","author":"Lee","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1021\/jo00013a044","article-title":"Nortopsentins A, B, and C. Cytotoxic and antifungal imidazolediylbis[indoles] from the sponge Spongosorites ruetzleri","volume":"56","author":"Sakemi","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1002\/cmdc.201100078","article-title":"Synthesis and antitumor activity of 3-(2-phenyl-1,3-thiazol-4-yl)-1h-indoles and 3-(2-phenyl-1,3-thiazol-4-yl)-1h-7-azaindoles","volume":"6","author":"Diana","year":"2011","journal-title":"ChemMedChem"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.2174\/09298673113206660307","article-title":"Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues","volume":"21","author":"Carbone","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"7060","DOI":"10.1021\/jm400842x","article-title":"Novel 1h-pyrrolo[2,3-b]pyridine derivative nortopsentin analogues: Synthesis and antitumor activity in peritoneal mesothelioma experimental models","volume":"56","author":"Carbone","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3390\/md13010460","article-title":"Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues","volume":"13","author":"Carbone","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/PPO.0000000000000138","article-title":"The contribution of angiogenesis to the process of metastasis","volume":"21","author":"Bielenberg","year":"2015","journal-title":"Cancer J."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/nature04479","article-title":"Endothelial cells and VEGF in vascular development","volume":"438","author":"Coultas","year":"2005","journal-title":"Nature"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"R217","DOI":"10.1016\/S1074-5521(99)80081-7","article-title":"Molecular angiogenesis","volume":"6","author":"Klagsbrun","year":"1999","journal-title":"Chem. Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.1158\/1078-0432.CCR-10-3109","article-title":"SKLB1002, a novel potent inhibitor of VEGF receptor 2 signaling, inhibits angiogenesis and tumor growth in vivo","volume":"17","author":"Zhang","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/sj.emboj.7600709","article-title":"VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis","volume":"24","author":"Matsumoto","year":"2005","journal-title":"EMBO J."},{"key":"ref_195","first-page":"1517","article-title":"Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma","volume":"26","author":"Nishi","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.med.49.1.407","article-title":"Angiogenesis and tumor metastasis","volume":"49","author":"Zetter","year":"1998","journal-title":"Annu. Rev. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1038\/sj.onc.1205552","article-title":"N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells","volume":"21","author":"Noujaim","year":"2002","journal-title":"Oncogene"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/CCO.0000000000000122","article-title":"Tumor-stroma crosstalk: Targeting stroma in breast cancer","volume":"26","author":"Criscitiello","year":"2014","journal-title":"Curr. Opin. Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1053\/j.seminoncol.2003.08.013","article-title":"A phase I\/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer","volume":"30","author":"Cobleigh","year":"2003","journal-title":"Semin. Oncol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2302\/kjm.61.47","article-title":"Tumor angiogenesis and anti-angiogenic therapy","volume":"61","author":"Kubota","year":"2012","journal-title":"Keio J. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1016\/j.bmcl.2011.10.023","article-title":"Stylissamide X, a new proline-rich cyclic octapeptide as an inhibitor of cell migration, from an indonesian marine sponge of Stylissa sp.","volume":"22","author":"Arai","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.foodchem.2013.03.038","article-title":"Matrix metalloproteinases (MMPs) inhibitory effects of an octameric oligopeptide isolated from abalone Haliotis discus hannai","volume":"141","author":"Nguyen","year":"2013","journal-title":"Food Chem."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.3390\/md10112492","article-title":"Subereamolline A as a potent breast cancer migration, invasion and proliferation inhibitor and bioactive dibrominated alkaloids from the red sea sponge Pseudoceratina arabica","volume":"10","author":"Shaala","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1021\/ja057404h","article-title":"Cortistatins A, B, C, and D, anti-angiogenic steroidal alkaloids, from the marine sponge Corticium simplex","volume":"128","author":"Aoki","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_205","first-page":"261","article-title":"Antiangiogenic activity of aeroplysinin-1, a brominated compound isolated from a marine sponge","volume":"16","author":"Carmona","year":"2002","journal-title":"FASEB J."},{"key":"ref_206","first-page":"6788","article-title":"Inhibition of tumor cell invasion and angiogenesis by motuporamines","volume":"61","author":"Roskelley","year":"2001","journal-title":"Cancer Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.3390\/molecules18033543","article-title":"Cyclic versus hemi-bastadins. Pleiotropic anti-cancer effects: From apoptosis to anti-angiogenic and anti-migratory effects","volume":"18","author":"Mathieu","year":"2013","journal-title":"Molecules"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"753524","DOI":"10.1155\/2014\/753524","article-title":"Emerging targets in pituitary adenomas: Role of the CXCL12\/CXCR4-R7 system","volume":"2014","author":"Barbieri","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/cb900240k","article-title":"Sceptrin, a marine natural compound, inhibits cell motility in a variety of cancer cell lines","volume":"5","author":"Cipres","year":"2010","journal-title":"ACS Chem. Biol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/cm.970130302","article-title":"Latrunculins\u2014Novel marine macrolides that disrupt microfilament organization and affect cell growth: I. Comparison with cytochalasin D","volume":"13","author":"Spector","year":"1989","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1021\/np050372r","article-title":"Bioactive natural and semisynthetic latrunculins","volume":"69","author":"Youssef","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1021\/np070587w","article-title":"Latrunculin A and its C-17-O-carbamates inhibit prostate tumor cell invasion and HIF-1 activation in breast tumor cells","volume":"71","author":"Sayed","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1124\/mol.105.019075","article-title":"The microtubule binding drug laulimalide inhibits vascular endothelial growth factor-induced human endothelial cell migration and is synergistic when combined with docetaxel (taxotere)","volume":"69","author":"Lu","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1631\/jzus.B1000217","article-title":"Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-\u03baB-dependent MMP-9 and VEGF expressions","volume":"12","author":"Zhao","year":"2011","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"H280","DOI":"10.1111\/j.1750-3841.2010.01837.x","article-title":"Differential effects of sulfated triterpene glycosides, holothurin A1, and 24-dehydroechinoside A, on antimetastasic activity via regulation of the MMP-9 signal pathway","volume":"75","author":"Zhao","year":"2010","journal-title":"J. Food Sci."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2011.06.023","article-title":"Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts","volume":"668","author":"Iratni","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/cmdc.201200516","article-title":"Optimization of marine triterpene sipholenols as inhibitors of breast cancer migration and invasion","volume":"8","author":"Foudah","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1016\/j.bmcl.2008.05.018","article-title":"Synthesis of BC-ring model of globostellatic acid X methyl ester, an anti-angiogenic substance from marine sponge","volume":"18","author":"Kotoku","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1016\/S0040-4039(00)91753-2","article-title":"Heteronemin, a new scalarin type sesterterpene from the sponge Heteronema Erecta","volume":"17","author":"Kazlauskas","year":"1976","journal-title":"Tetrahedron Lett."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1007\/s00204-013-1045-1","article-title":"In vitro characterisation of the anti-intravasative properties of the marine product heteronemin","volume":"87","author":"Kopf","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1016\/S0040-4020(01)97451-4","article-title":"Sarcophine, a new epoxy cembranolide from marine origin","volume":"30","author":"Bernstein","year":"1974","journal-title":"Tetrahedron"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1021\/np050527v","article-title":"Biocatalytic and antimetastatic studies of the marine cembranoids sarcophine and 2-epi-16-deoxysarcophine","volume":"69","author":"Sawant","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.1016\/j.bmc.2011.06.060","article-title":"Semisynthetic analogues of the marine cembranoid sarcophine as prostate and breast cancer migration inhibitors","volume":"19","author":"Hassan","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1021\/np800208k","article-title":"Sinulodurins A and B, antiproliferative and anti-invasive diterpenes from the soft coral Sinularia dura","volume":"71","author":"Radwan","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1021\/np0340246","article-title":"Strongylophorine-26, a new meroditerpenoid isolated from the marine sponge Petrosia (Strongylophora) corticata that exhibits anti-invasion activity","volume":"67","author":"Warabi","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3390\/md9020154","article-title":"Antiproliferative and antiangiogenic activities of smenospongine, a marine sponge sesquiterpene aminoquinone","volume":"9","author":"Kong","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1016\/j.ejmech.2010.09.067","article-title":"A neuroprotective sulfone of marine origin and the in vivo anti-inflammatory activity of an analogue","volume":"45","author":"Wen","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.intimp.2010.05.002","article-title":"Polyacetylenediols regulate the function of human monocyte-derived dendritic cells","volume":"10","author":"Takei","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_229","first-page":"153","article-title":"Mitogen-activated protein (map) kinase pathways: Regulation and physiological functions","volume":"22","author":"Pearson","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cellsig.2008.11.013","article-title":"Protein scaffolds in map kinase signalling","volume":"21","author":"Brown","year":"2009","journal-title":"Cell Signal."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0960-0760(01)00189-3","article-title":"The role of mitogen-activated protein (map) kinase in breast cancer","volume":"80","author":"Santen","year":"2002","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.bbamcr.2006.11.006","article-title":"Map kinase pathways: The first twenty years","volume":"1773","author":"Avruch","year":"2007","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc969","article-title":"Targeting ras signalling pathways in cancer therapy","volume":"3","author":"Downward","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrc2110","article-title":"Protein kinase c and other diacylglycerol effectors in cancer","volume":"7","author":"Griner","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1158\/1078-0432.CCR-12-0662","article-title":"The PI3K\/AKT\/mTOR pathway as a therapeutic target in endometrial cancer","volume":"18","author":"Slomovitz","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"16052","DOI":"10.1074\/jbc.M111.223602","article-title":"Mitochondrial c-Jun N-terminal kinase (JNK) signaling initiates physiological changes resulting in amplification of reactive oxygen species generation","volume":"286","author":"Chambers","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1042\/BJ20100323","article-title":"Mechanisms and functions of p38 MAPK signalling","volume":"429","author":"Cuadrado","year":"2010","journal-title":"Biochem. J."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd2541","article-title":"High-throughput kinase profiling as a platform for drug discovery","volume":"7","author":"Goldstein","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1172\/JCI76094","article-title":"Targeting cancer with kinase inhibitors","volume":"125","author":"Gross","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.3390\/md9102131","article-title":"Kinase inhibitors from marine sponges","volume":"9","author":"Skropeta","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1021\/jm0102856","article-title":"Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1)","volume":"45","author":"Tasdemir","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1021\/np049763g","article-title":"A madagascar sponge Batzella sp. As a source of alkylated iminosugars","volume":"68","author":"Segraves","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1081\/CNV-120025095","article-title":"Bryostatin-1: A novel PKC inhibitor in clinical development","volume":"21","author":"Kortmansky","year":"2003","journal-title":"Cancer Investig."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"6327","DOI":"10.1021\/jo00049a049","article-title":"11-hydroxystaurosporine: A highly cytotoxic, powerful protein kinase C inhibitor from a tunicate","volume":"57","author":"Kinnel","year":"1992","journal-title":"J. Org. Chem."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1124\/jpet.109.155531","article-title":"Early effects of lasonolide A on pancreatic cancer cells","volume":"331","author":"Isbrucker","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1016\/S0960-894X(01)80407-8","article-title":"Penazetidine A, an alkaloid inhibitor of protein kinase C","volume":"4","author":"Alvi","year":"1994","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1021\/ol052744t","article-title":"Liphagal, a selective inhibitor of PI3 kinase \u03b1 isolated from the sponge akacoralliphaga: Structure elucidation and biomimetic synthesis","volume":"8","author":"Marion","year":"2006","journal-title":"Org. Lett."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"8523","DOI":"10.1021\/jm100531u","article-title":"Synthesis of phosphatidylinositol 3-kinase (PI3K) inhibitory analogues of the sponge meroterpenoid liphagal","volume":"53","author":"Pereira","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1021\/ol101173w","article-title":"Enantioselective total synthesis of the selective PI3 kinase inhibitor liphagal","volume":"12","author":"Chahboun","year":"2010","journal-title":"Org. Lett."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1016\/j.bbagen.2013.07.011","article-title":"Dolastatin, along with Celecoxib, stimulates apoptosis by a mechanism involving oxidative stress, membrane potential change and PI3-K\/AKT pathway down regulation","volume":"1830","author":"Piplani","year":"2013","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1124\/mol.105.011361","article-title":"Kahalalide F induces necrosis-like cell death that involves depletion of ErbB3 and inhibition of Akt signaling","volume":"68","author":"Janmaat","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"5353","DOI":"10.1158\/1078-0432.CCR-10-1948","article-title":"PM02734 (elisidepsin) induces caspase-independent cell death associated with features of autophagy, inhibition of the Akt\/mTOR signaling pathway, and activation of death-associated protein kinase","volume":"17","author":"Ling","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.1038\/sj.onc.1205972","article-title":"Aplidin\u2122 induces the mitochondrial apoptotic pathway via oxidative stress-mediated JNK and p38 activation and protein kinase C \u03b4","volume":"21","author":"Losada","year":"2002","journal-title":"Oncogene"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1349-7006.2005.00055.x","article-title":"Inhibition of protein synthesis and activation of stress-activated protein kinases by onnamide A and theopederin B, antitumor marine natural products","volume":"96","author":"Lee","year":"2005","journal-title":"Cancer Sci."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-genom-090413-025552","article-title":"Translating genomics for precision cancer medicine","volume":"15","author":"Roychowdhury","year":"2014","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.2147\/DDDT.S93449","article-title":"In silico approach for the discovery of new PPAR\u03b3 modulators among plant-derived polyphenols","volume":"9","author":"Encinar","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.2147\/DDDT.S117369","article-title":"Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach","volume":"10","author":"Galiano","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jconrel.2013.04.020","article-title":"Oral delivery of anticancer drugs: Challenges and opportunities","volume":"170","author":"Thanki","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_259","unstructured":"(2017, June 22). ADMET Profile for Antineoplasic Drugs. Available online: http:\/\/dockingfiles.umh.es\/anticancer-drugs\/Anticancer_drugslist.asp."},{"key":"ref_260","unstructured":"(2017, June 22). Marine Natural Library Molecular Docking Site. Available online: http:\/\/docking.umh.es\/chemlib\/mnplib."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.4155\/fmc.11.118","article-title":"Marine natural products: A new wave of drugs?","volume":"3","author":"Montaser","year":"2011","journal-title":"Future Med. Chem."},{"key":"ref_262","doi-asserted-by":"crossref","unstructured":"Blunt, J., and Munro, M.H.G. (2008). Dictionary of Marine Natural Products, with CD-ROM, Chapman & Hall\/CRC.","DOI":"10.1201\/9780849382178"},{"key":"ref_263","unstructured":"(2017, June 22). National Institutes of Health (NIH) Chemical Identifier Resolution Service, Available online: https:\/\/cactus.nci.nih.gov\/chemical\/structure."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13321-016-0188-5","article-title":"NPCARE: Database of natural products and fractional extracts for cancer regulation","volume":"9","author":"Choi","year":"2017","journal-title":"J. Cheminform."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2015.12.002","article-title":"Developing natural product drugs: Supply problems and how they have been overcome","volume":"162","author":"Newman","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.foodchem.2013.07.027","article-title":"Bioactive compounds from marine mussels and their effects on human health","volume":"142","author":"Grienke","year":"2014","journal-title":"Food Chem."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.marpolbul.2016.06.091","article-title":"Chemical contaminants entering the marine environment from sea-based sources: A review with a focus on european seas","volume":"112","author":"Tornero","year":"2016","journal-title":"Mar. Pollut. Bull."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.tibtech.2013.06.004","article-title":"Coral aquaculture to support drug discovery","volume":"31","author":"Leal","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1039\/b808331m","article-title":"Development of yondelis\u00ae (trabectedin, ET-743). A semisynthetic process solves the supply problem","volume":"26","author":"Cuevas","year":"2009","journal-title":"Nat. Prod. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1037\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:40:11Z","timestamp":1760208011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,23]]},"references-count":270,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["molecules22071037"],"URL":"https:\/\/doi.org\/10.3390\/molecules22071037","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,23]]}}}