{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:27:52Z","timestamp":1772659672873,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling.  A Quantitative Structure\u2013Activity Relationship approach, for classification, was used for the prediction of active\/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened\u201457 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.<\/jats:p>","DOI":"10.3390\/md12020757","type":"journal-article","created":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T03:27:01Z","timestamp":1390879621000},"page":"757-778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs"],"prefix":"10.3390","volume":"12","author":[{"given":"Florbela","family":"Pereira","sequence":"first","affiliation":[{"name":"CQFB (Centro de Qu\u00edmica Fina e Biotecnologia)\/REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa Campus Caparica,  Caparica 2829-516, Portugal"}]},{"given":"Diogo","family":"Latino","sequence":"additional","affiliation":[{"name":"CQFB (Centro de Qu\u00edmica Fina e Biotecnologia)\/REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa Campus Caparica,  Caparica 2829-516, Portugal"},{"name":"CCMM (Centro de Ci\u00eancias Moleculares e Materiais), Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universida Lisboa, Campo Grande, Lisboa 1749-016, Portugal"}]},{"given":"Susana","family":"Gaud\u00eancio","sequence":"additional","affiliation":[{"name":"CQFB (Centro de Qu\u00edmica Fina e Biotecnologia)\/REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa Campus Caparica,  Caparica 2829-516, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.drudis.2008.07.004","article-title":"Natural products in drug discovery","volume":"13","author":"Harvey","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1016\/j.bbagen.2013.02.008","article-title":"Natural products: A continuing source of novel drug leads","volume":"1830","author":"Cragg","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","unstructured":"MarinLit. Available online:http:\/\/www.chem.canterbury.ac.nz\/marinlit\/marinlit.shtml."},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"17272","DOI":"10.1073\/pnas.0503647102","article-title":"Charting biologically relevant chemical space: A structural classification of natural products (SCONP)","volume":"102","author":"Koch","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/ci700286x","article-title":"Natural product-likeness score and its application for prioritization of compound libraries","volume":"46","author":"Ertl","year":"2008","journal-title":"J. Chem. Inf. Model."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10800","DOI":"10.1002\/anie.201007004","article-title":"Biology-oriented synthesis","volume":"50","author":"Wetzel","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/jcc.20186","article-title":"SARS-CoV protease inhibitors design using virtual screening method from natural products libraries","volume":"26","author":"Liu","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1021\/np050510c","article-title":"Biological activities and 3D QSAR studies of a series of Delisea pulchra (cf. fimbriata) derived natural products","volume":"69","author":"Wright","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10822-009-9307-y","article-title":"Molecular docking and QSAR of aplyronine A and analogues: Potent inhibitors of actin","volume":"24","author":"Hussain","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.ejmech.2011.01.028","article-title":"Design of semisynthetic analogues and 3D-QSAR study of eunicellin-based diterpenoids as prostate cancer migration and invasion Inhibitors","volume":"46","author":"Hassan","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1021\/np8002222","article-title":"Evolving trends in the dereplication of natural product extracts: New methodology for rapid, small-scale investigation of natural product extracts","volume":"71","author":"Lang","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_14","unstructured":"Blunt, J.W., Munro, M.H.G., and Laatsch, H. (2007). AntiMarin Database, University of G\u00f6ttingen."},{"key":"ref_15","unstructured":"AntiBase Home Page. Available online:http:\/\/wwwuser.gwdg.de\/~hlaatsc\/antibase.htm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ja.2005.1","article-title":"Bioactive microbial metabolites","volume":"58","year":"2005","journal-title":"J. Antibiot."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.7164\/antibiotics.35.692","article-title":"Deoxy derivatives of butirosin A and 5\u2032-amino-5\u2032-deoxybutirosin A, aminoglycoside antibiotics resistant to bacterial 3\u2032-phosphorylative enzymatic inactivation. Synthesis and NMR studies","volume":"35","author":"Woo","year":"1982","journal-title":"J. Antibiot."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1128\/AAC.43.4.727","article-title":"Aminoglycosides: Activity and resistance","volume":"43","author":"Glupczynski","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","first-page":"1328","article-title":"Genistein arrests cell cycle progression at G2-M","volume":"53","author":"Matsukawa","year":"1993","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/BF02978247","article-title":"Antitumor triterpenes from medicinal plants","volume":"17","author":"Ryu","year":"1994","journal-title":"Arch. Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0304-3835(98)00141-4","article-title":"Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids","volume":"130","author":"Varnat","year":"1998","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0304-3835(92)90145-L","article-title":"Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-C7 cells","volume":"67","author":"Post","year":"1992","journal-title":"Cancer Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0378-8741(03)00192-2","article-title":"Cytotoxic effect of Plantago spp. on cancer cell lines","volume":"88","author":"Ayuso","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/BF01949895","article-title":"Cortinarins in Cortinarius speciosissimus? A critical revision","volume":"47","author":"Matthies","year":"1991","journal-title":"Experientia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6206","DOI":"10.1158\/1078-0432.CCR-11-0736","article-title":"Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism","volume":"17","author":"Fath","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/10826060701199122","article-title":"Microbiaeratin, a new natural indole alkaloid from a microbispora aerata strain, isolated from Livingston Island, Antarctica","volume":"37","author":"Ivanova","year":"2007","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1111\/j.1751-1097.2011.00993.x","article-title":"Photosensitization reactions in vitro and in vivo","volume":"87","author":"Kruft","year":"2011","journal-title":"Photochem. Photobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3390\/md7020210","article-title":"Antitumor compounds from marine actinomycetes","volume":"7","author":"Olano","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1021\/ol800527p","article-title":"Synthesis of eudistomin C and E: Improved preparation of the indole unit","volume":"10","author":"Yamagishi","year":"2008","journal-title":"Org. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1021\/np700740a","article-title":"Aurocitrin and related metabolites from the wood-decay fungus Hypocrea sp.","volume":"71","author":"Berkaew","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_32","unstructured":"PubChem Bioassay Web Page Cerulomycin\u2014Compound Summary. Available online:http:\/\/pubchem.ncbi.nlm.nih.gov\/summary\/summary.cgi?cid=5381230."},{"key":"ref_33","unstructured":"PubChem Bioassay Web Page Pyrrolnitrin\u2014Compound Summary. Available online:http:\/\/pubchem.ncbi.nlm.nih.gov\/summary\/summary.cgi?cid=13916."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1021\/np970430b","article-title":"5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from atractylodes lancea","volume":"61","author":"Resch","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4103\/0973-7847.70902","article-title":"Free radicals, antioxidants and functional foods: Impact on human health","volume":"4","author":"Lobo","year":"2010","journal-title":"Phcog. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1021\/np800064w","article-title":"Isolation, structure elucidation, and synthesis of cytotoxic tryptanthrin analogues from phaius mishmensis","volume":"71","author":"Jao","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.canlet.2011.07.008","article-title":"The antimitogenic effect of the cannabinoid receptor agonist WIN55212\u20132 on human melanoma cells is mediated by the membrane lipid raft","volume":"310","author":"Scuderi","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.7164\/antibiotics.30.11","article-title":"Isolation and characterization of a nucleoside antibiotic, amipurimycin","volume":"30","author":"Harada","year":"1977","journal-title":"J. Antibiot."},{"key":"ref_39","first-page":"1839","article-title":"Isolation of two streptothricin-like antibiotics, Nos. 6241-A and B, as inhibitors of de novo starch synthesis and their herbicidal activity","volume":"49","author":"Kida","year":"1985","journal-title":"Agric. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"433","DOI":"10.7164\/antibiotics.38.433","article-title":"5\u2032-Hydroxy-2\u2032-N-demethyl-dihydrostreptomycin produced by a streptomyces","volume":"38","author":"Kondo","year":"1985","journal-title":"J. Antibiot."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1021\/ja00056a048","article-title":"Polycavernoside A: A novel glycosidic macrolide from the red alga Polycavernosa tsudai (Gracilaria edulis)","volume":"115","author":"Haddock","year":"1993","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1021\/ac00220a013","article-title":"Development and use of charged partial surface area structural descriptors in computer assisted quantitative structure property relationship studies","volume":"62","author":"Stanton","year":"1990","journal-title":"Anal. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1021\/jm000942e","article-title":"Fast Calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport Properties","volume":"43","author":"Ertl","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1021\/ci050049u","article-title":"Application of the random forest method in studies of local lymph node assay based skin sensitization data","volume":"45","author":"Li","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/ci980137x","article-title":"Metric validation and the receptor relevant subspace concept","volume":"39","author":"Pearlman","year":"1999","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Todeschini, R., and Consonni, V. (2009). Molecular Descriptors for Chemoinformatics, WILEY-VCH.","DOI":"10.1002\/9783527628766"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1021\/jo201562f","article-title":"Estimation of mayr electrophilicity with a quantitative structure\u2013property relationship approach using empirical and DFT descriptors","volume":"76","author":"Pereira","year":"2011","journal-title":"J. Org. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1021\/ci600563w","article-title":"Ensemble feature selection: Consistent descriptor subsets for multiple QSAR models","volume":"47","author":"Dutta","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1093-3263(02)00187-0","article-title":"Prediction of dihydrofolate reductase inhibition and selectivity using computational neural network and linear discriminant analysis","volume":"21","author":"Mattioni","year":"2003","journal-title":"J. Mol. Graph. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6924","DOI":"10.3390\/ijms13066924","article-title":"Development of classification models for identifying \u201ctrue\u201d p-glycoprotein (p-gp) inhibitors through inhibition, ATPase activation and monolayer efflux assays","volume":"13","author":"Rapposelli","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1021\/ci6002619","article-title":"Classification of highly unbalanced CYP450 data of drugs using cost sensitive machine learning techniques","volume":"47","author":"Eitrich","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1021\/jm801389m","article-title":"Topological polar surface area defines substrate transport by multidrug resistance associated protein 1 (MRP1\/ABCC1)","volume":"52","author":"Fernandes","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_53","unstructured":"PubChem Home Page Available online:http:\/\/pubchem.ncbi.nlm.nih.gov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D400","DOI":"10.1093\/nar\/gkr1132","article-title":"PubChem\u2019s bioAssay database","volume":"40","author":"Wang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_55","unstructured":"CDK Descriptor Calculator, Version 1.3.2. Available online:http:\/\/cdk.sourceforge.net\/."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.2174\/138161206777585274","article-title":"Recent developments of the chemistry development kit (CDK)\u2014An open-source java library for chemo- and bioinformatics","volume":"12","author":"Steinbeck","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Autom. Control"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA data mining software: An update","volume":"11","author":"Hall","year":"2009","journal-title":"SIGKDD Explor."},{"key":"ref_59","unstructured":"Weka. Available online:http:\/\/www.cs.waikato.ac.nz\/ml\/weka\/."},{"key":"ref_60","unstructured":"Hall, M.A., and Smith, L.A. (1999, January 1\u20135). Correlation-based feature selection for machine learning. In. Proceedings of the Twelfth International FLAIRS Conference, Orlando, FL, USA."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF00153759","article-title":"Instance-based learning algorithms","volume":"6","author":"Aha","year":"1991","journal-title":"Mach. Learn."},{"key":"ref_62","unstructured":"Breiman, L., Friedman, J.H., Olshen, R.A., and Stone, C.J. (2000). Classification and Regression Trees, Chapman & Hall\/CRC."},{"key":"ref_63","unstructured":"R Development Core Team Available online:http:\/\/www.r-project.org\/."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00994018","article-title":"Support vector networks","volume":"20","author":"Cortes","year":"1995","journal-title":"Mach. Learn."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/1961189.1961199","article-title":"LIBSVM: A library for support vector machines","volume":"2","author":"Chang","year":"2011","journal-title":"ACM Trans. Intell. Syst. Technol."},{"key":"ref_67","unstructured":"LIBSVM. Available online:http:\/\/www.csie.ntu.edu.tw\/~cjlin\/libsvm\/."},{"key":"ref_68","unstructured":"El Manzalawy, Y., and Honavar, V. WLSVM: Integrating LibSVM into Weka Environment. Available online:http:\/\/www.cs.iastate.edu\/~yasser\/wlsvm\/."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/2\/757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:07:43Z","timestamp":1760216863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/2\/757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,27]]},"references-count":68,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2]]}},"alternative-id":["md12020757"],"URL":"https:\/\/doi.org\/10.3390\/md12020757","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,27]]}}}