{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:42:09Z","timestamp":1773866529516,"version":"3.50.1"},"reference-count":90,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020|UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020|UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["2022.02910.PTDC"],"award-info":[{"award-number":["2022.02910.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["DDC"],"abstract":"<jats:p>The indole scaffold is considered a privileged framework in the design and synthesis of several active pharmaceutical ingredients, particularly as promising anticancer agents. Its presence in several bioactive natural compounds has caught the attention of the scientific community, which has been committed to unveiling its biosynthetic pathways and generating multiple derivatives with innovative synthetic routes. The large variety of structural derivatives enhances their use in multiple bioapplications and pharmacological activities. In this review, the reader will have easy access to some examples of natural and synthetic indole derivatives with antimicrobial, antidepressant, anti-inflammatory, antiviral, antimigraine, and antiemetic activity. However, the main topic of this review is related to cancer and the importance of indole derivatives as promising anticancer drugs. Two of the reasons why cancer is considered a massive problem worldwide are attributed to the struggle to develop target-specific drugs while avoiding drug resistance. Among countless drugs targeting specific proteins involved in tumorigenesis, prompting life quality in the treatment of several cancer types, protein kinases, desoxyribonucleic acid topoisomerases, and P-glycoprotein have been shown to be the main targets when it comes to the development of novel anticancer agents. Furthermore, indole and its derivatives are also studied regarding affinity to other targets related to cancer. This review aims to highlight the utility of the indole scaffold in anticancer drug design, inspiring the creation and synthesis of new derivatives that target specific proteins and address drug resistance challenges.<\/jats:p>","DOI":"10.3390\/ddc3030029","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T14:16:38Z","timestamp":1721398598000},"page":"488-511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biological Profile of Synthetic and Natural Indole Derivatives: Paving New Paths in Cancer Treatment"],"prefix":"10.3390","volume":"3","author":[{"given":"Ana Margarida","family":"Janeiro","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-7871","authenticated-orcid":false,"given":"Carolina S.","family":"Marques","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Institute for Advanced Studies and Research, University of \u00c9vora, Rua Rom\u00e3o Ramalho, 59, 7000-641 \u00c9vora, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dhuguru, J., and Skouta, R. (2020). Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents. Molecules, 25.","DOI":"10.3390\/molecules25071615"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12069","DOI":"10.1039\/C7RA13321A","article-title":"Recent advances in the application of indoles in multicomponent reactions","volume":"8","author":"Moradi","year":"2018","journal-title":"RSC Adv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bandini, M. (2013). Electrophilicity: The \u201cdark-side\u201d of indole chemistry. Org. Biomol. Chem., 11.","DOI":"10.1039\/c3ob40735g"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1016\/j.apsb.2022.03.021","article-title":"Target-based anticancer indole derivatives and insight into structure\u2013activity relationship: A mechanistic review update (2018\u20132021)","volume":"12","author":"Dhiman","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100119","DOI":"10.1016\/j.crphar.2022.100119","article-title":"Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents","volume":"3","author":"Bajad","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Islam, F., Dehbia, Z., Zehravi, M., Das, R., Sivakumar, M., Krishnan, K., Billah, A.A.M., Bose, B., Ghosh, A., and Paul, S. (2023). Indole alkaloids from marine resources: Understandings from therapeutic point of view to treat cancers. Chem. Biol. Interact., 383.","DOI":"10.1016\/j.cbi.2023.110682"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Piechowska, P., Zawirska-Wojtasiak, R., and Mildner-Szkudlarz, S. (2019). Bioactive \u03b2-Carbolines in Food: A Review. Nutrients, 11.","DOI":"10.3390\/nu11040814"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dewick, P.M. (2009). Medicinal Natural Products: A Biosynthetic Approach, John Wiley & Sons Ltd.. [3rd ed.].","DOI":"10.1002\/9780470742761"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bbr.2014.07.037","article-title":"Serotonin in Parkinson\u2019s disease","volume":"277","author":"Politis","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.3233\/ADR-230070","article-title":"Mitochondrial Interaction with Serotonin in Neurobiology and Its Implication in Alzheimer\u2019s Disease","volume":"7","author":"Tian","year":"2023","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Szab\u00f3, T., Volk, B., and Milen, M. (2021). Recent Advances in the Synthesis of \u03b2-Carboline Alkaloids. Molecules, 26.","DOI":"10.3390\/molecules26030663"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.sajb.2023.08.034","article-title":"Biosynthesis, extraction, detection and pharmacological attributes of vinblastine and vincristine, two important chemotherapeutic alkaloids of Catharanthus roseus (L.) G. Don: A review","volume":"161","author":"Paul","year":"2023","journal-title":"S. Afr. J. Bot."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1039\/C9QO01315F","article-title":"Recent advances in the synthesis of indoles from alkynes and nitrogen sources","volume":"7","author":"Neto","year":"2020","journal-title":"Org. Chem. Front."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bilal, M., Rasool, N., Khan, S.G., Rashid, U., Altaf, H., and Ali, I. (2021). Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts. Catalysts, 11.","DOI":"10.3390\/catal11091018"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kumari, A., and Singh, R.K. (2019). Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg. Chem., 89.","DOI":"10.1016\/j.bioorg.2019.103021"},{"key":"ref_17","unstructured":"Leimgruber, B.W. (2016). Leimgruber\u2013Batcho Indole Synthesis. Indole Ring Synthesis, Wiley."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0040-4039(00)84114-3","article-title":"Synthesis of indoles from N-aryl-1-alkenylsulphinamides","volume":"27","author":"Baudin","year":"1986","journal-title":"Tetrahedron Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/cber.188301602141","article-title":"Ueber die Hydrazine der Brenztraubens\u00e4ure","volume":"16","author":"Fischer","year":"1883","journal-title":"Berichte Dtsch. Chem. Ges."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/cber.189703001200","article-title":"Einwirkung von Oxalester und Natrium\u00e4thylat auf Nitrotoluole. Synthese nitrirter Phenylbrenztraubens\u00e4uren","volume":"30","author":"Reissert","year":"1897","journal-title":"Berichte Dtsch. Chem. Ges."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/cber.186900201268","article-title":"Synthese des Indols","volume":"2","author":"Baeyer","year":"1869","journal-title":"Berichte Dtsch. Chem. Ges."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1016\/j.tetlet.2009.05.027","article-title":"Straightforward selective preparation of nitro- or amino-indoles from 2-halonitroanilines and alkynes. First synthesis of 7-amino-5-nitroindoles","volume":"50","author":"Sanz","year":"2009","journal-title":"Tetrahedron Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1016\/j.tetlet.2012.06.023","article-title":"Copper catalysed domino decarboxylative cross coupling-cyclisation reactions: Synthesis of 2-arylindoles","volume":"53","author":"Ponpandian","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1002\/adsc.201600804","article-title":"Commercial Supported Gold Nanoparticles Catalyzed Alkyne Hydroamination and Indole Synthesis","volume":"358","author":"Liang","year":"2016","journal-title":"Adv. Synth. Catal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1002\/cber.191204501160","article-title":"\u00dcber eine neue Darstellungsweise f\u00fcr substituierte Indole. I","volume":"45","author":"Madelung","year":"1912","journal-title":"Berichte Dtsch. Chem. Ges."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/S0040-4039(01)93730-X","article-title":"The reaction of vinyl grignard reagents with 2-substituted nitroarenes: A new approach to the synthesis of 7-substituted indoles","volume":"30","author":"Bartoli","year":"1989","journal-title":"Tetrahedron Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1021\/ja00017a059","article-title":"Synthesis of indoles via palladium-catalyzed heteroannulation of internal alkynes","volume":"113","author":"Larock","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1021\/ja00086a054","article-title":"A Novel Tin-Mediated Indole Synthesis","volume":"116","author":"Fukuyama","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106552","DOI":"10.1016\/j.phrs.2022.106552","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update","volume":"187","author":"Roskoski","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2016.05.025","article-title":"Indoles\u2014A promising scaffold for drug development","volume":"91","author":"Sravanthi","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2147\/JEP.S180777","article-title":"In vitro pharmacological characterization of SPN-810M (molindone)","volume":"10","author":"Yu","year":"2018","journal-title":"J. Exp. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: The DrugBank Knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Omar, F., Tareq, A.M., Alqahtani, A.M., Dhama, K., Sayeed, M.A., Emran, T.B., and Simal-Gandara, J. (2021). Plant-Based Indole Alkaloids: A Comprehensive Overview from a Pharmacological Perspective. Molecules, 26.","DOI":"10.3390\/molecules26082297"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejmech.2017.04.003","article-title":"Indoles as therapeutics of interest in medicinal chemistry: Bird\u2019s eye view","volume":"134","author":"Chadha","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1016\/j.arabjc.2015.05.015","article-title":"Synthesis, characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study","volume":"12","author":"Choppara","year":"2019","journal-title":"Arab. J. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/j.bmc.2015.02.037","article-title":"Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation","volume":"23","author":"Mielczarek","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D1307","DOI":"10.1093\/nar\/gkab918","article-title":"NCATS Inxight Drugs: A comprehensive and curated portal for translational research","volume":"50","author":"Siramshetty","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bhat, M.A., Al-Omar, M.A., Raish, M., Ansari, M.A., Abuelizz, H.A., Bakheit, A.H., and Naglah, A.M. (2018). Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies. Molecules, 23.","DOI":"10.3390\/molecules23061250"},{"key":"ref_39","first-page":"157","article-title":"Capsaicin Derivatives Containing Indole and Nitroindole for Improved Anti-Inflammatory Activity","volume":"26","author":"Mukthung","year":"2018","journal-title":"Naresuan Univ. J. Sci. Technology."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Girgis, A.S., Panda, S.S., Kariuki, B.M., Bekheit, M.S., Barghash, R.F., and Aboshouk, D.R. (2023). Indole-Based Compounds as Potential Drug Candidates for SARS-CoV-2. Molecules, 28.","DOI":"10.20944\/preprints202308.0746.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/1541-7786.MCR-23-0411","article-title":"Updating the Definition of Cancer","volume":"21","author":"Brown","year":"2023","journal-title":"Mol. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1016\/S2214-109X(19)30488-7","article-title":"Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis","volume":"8","author":"Georges","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hanselmann, R.G., and Welter, C. (2016). Origin of Cancer: An Information, Energy, and Matter Disease. Front. Cell Dev. Biol., 4.","DOI":"10.3389\/fcell.2016.00121"},{"key":"ref_44","unstructured":"Kufe, D.W., Pollock, R.E., Weichselbaum, R.R., Bast, R.C., Gansler, T.S., Holland, J.F., and Frei, E. (2003). Multistage Carcinogenes. Cancer Medicine, BC Decker Inc.. [6th ed.]."},{"key":"ref_45","unstructured":"Bochicchio, A., Zayatz, E., Mickey, R.K., Harik, L., and Ej Publishing Services (2014). Multi-step Tumorigenesis. The Biology of CANCER, Garland Science, Taylor & Francis Group, LLC. [2nd ed.]."},{"key":"ref_46","unstructured":"Baba, A.I., and C\u00e2toi, C. (2007). Tumor Cell Morphology. Comparative Oncology, The Publishing House of the Romanian Academy."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-319-43624-1_7","article-title":"The Role of DNA Methylation in Cancer","volume":"Volume 945","author":"Lakshminarasimhan","year":"2016","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Srinivas, U.S., Tan, B.W.Q., Vellayappan, B.A., and Jeyasekharan, A.D. (2019). ROS and the DNA damage response in cancer. Redox Biol., 25.","DOI":"10.1016\/j.redox.2018.101084"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"a006098","DOI":"10.1101\/cshperspect.a006098","article-title":"Signal Transduction in Cancer","volume":"5","author":"Sever","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Khetmalis, Y.M., Shivani, M., Murugesan, S., and Chandra Sekhar, K.V.G. (2021). Oxindole and its derivatives: A review on recent progress in biological activities. Biomed. Pharmacother., 141.","DOI":"10.1016\/j.biopha.2021.111842"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1146\/annurev-biochem-090308-173656","article-title":"The Evolution of Protein Kinase Inhibitors from Antagonists to Agonists of Cellular Signaling","volume":"80","author":"Dar","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7150\/ijms.1.101","article-title":"Tyrosine kinase\u2014Role and significance in Cancer","volume":"1","author":"Paul","year":"2004","journal-title":"Int. J. Med. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Salerno, S., Barresi, E., Baglini, E., Poggetti, V., Da Settimo, F., and Taliani, S. (2023). Target-Based Anticancer Indole Derivatives for the Development of Anti-Glioblastoma Agents. Molecules, 28.","DOI":"10.3390\/molecules28062587"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100929","DOI":"10.1016\/j.drup.2023.100929","article-title":"Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers","volume":"67","author":"Jin","year":"2023","journal-title":"Drug Resist. Updates"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hong, Y., Zhu, Y.Y., He, Q., and Gu, S.X. (2022). Indole derivatives as tubulin polymerization inhibitors for the development of promising anticancer agents. Bioorg. Med. Chem., 55.","DOI":"10.1016\/j.bmc.2021.116597"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ejmech.2014.11.007","article-title":"Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives","volume":"97","author":"Sherer","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1177\/2040620717721459","article-title":"Midostaurin: A novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis","volume":"8","author":"Gallogly","year":"2017","journal-title":"Ther. Adv. Hematol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"112359","DOI":"10.1016\/j.ejmech.2020.112359","article-title":"Current scenario of indole derivatives with potential anti-drug-resistant cancer activity","volume":"200","author":"Jia","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Christodoulou, M.S., Nicoletti, F., Mangano, K., Chiacchio, M.A., Facchetti, G., Rimoldi, I., Beccalli, E.M., and Giofr\u00e8, S. (2020). Novel 3,3-disubstituted oxindole derivatives. Synthesis and evaluation of the anti-proliferative activity. Bioorg. Med. Chem. Lett., 30.","DOI":"10.1016\/j.bmcl.2019.126845"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.bmcl.2004.01.050","article-title":"Meridianins, a new family of protein kinase inhibitors isolated from the Ascidian Aplidium meridianum","volume":"14","author":"Gompel","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1080\/10406638.2022.2101486","article-title":"Synthesis, In Vitro and in Cell Study of a New Spirooxindoles-Based N-Alkylated Maleimides Targeting HER2\/3 Signaling Pathway","volume":"43","author":"Barakat","year":"2023","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_62","first-page":"e202300185","article-title":"Synthesis and SARs study of novel spiro-oxindoles as potent antiproliferative agents with CDK-2 inhibitory activities","volume":"356","author":"Islam","year":"2023","journal-title":"Arch. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Dubba, A., and Kumar Koppula, S. (2024). Synthesis of Indole-Oxadiazole coupled isoxazole hybrids as potent EGFR targeting anticancer agents. Chem. Biol. Lett., 11.","DOI":"10.62110\/sciencein.cbl.2024.v11.651"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Bush, N.G., Evans-Roberts, K., and Maxwell, A. (2015). DNA Topoisomerases. EcoSal Plus, 6.","DOI":"10.1128\/ecosalplus.esp-0010-2014"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev.biochem.70.1.369","article-title":"DNA Topoisomerases: Structure, Function, and Mechanism","volume":"70","author":"Champoux","year":"2001","journal-title":"Annu. Rev. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.1021\/acs.jmedchem.1c02026","article-title":"Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy","volume":"65","author":"Wu","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"16099","DOI":"10.1021\/acs.jmedchem.2c01352","article-title":"Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment","volume":"65","author":"Zhang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.2147\/OTT.S114714","article-title":"Rucaparib: The past, present, and future of a newly approved PARP inhibitor for ovarian cancer","volume":"10","author":"Dockery","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.21037\/tcr-20-682","article-title":"A review of research progress of antitumor drugs based on tubulin targets","volume":"9","author":"Cheng","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Parker, A.L., Kavallaris, M., and McCarroll, J.A. (2014). Microtubules and Their Role in Cellular Stress in Cancer. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00153"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"R764","DOI":"10.1016\/j.cub.2007.07.002","article-title":"Microtubule Polymerization: One Step at a Time","volume":"17","author":"Sept","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12935-022-02624-9","article-title":"Anticancer potential of alkaloids: A key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine","volume":"22","author":"Dhyani","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13045-022-01350-z","article-title":"Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: From molecular mechanisms to potential therapeutic targets","volume":"15","author":"Qin","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1021\/acs.jmedchem.6b00021","article-title":"Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo","volume":"59","author":"Yan","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Romagnoli, R., Prencipe, F., Oliva, P., Kimatrai Salvador, M., Brancale, A., Ferla, S., Hamel, E., Viola, G., Bortolozzi, R., and Persoons, L. (2020). Design, synthesis and biological evaluation of 2-alkoxycarbonyl-3-anilinoindoles as a new class of potent inhibitors of tubulin polymerization. Bioorg. Chem., 97.","DOI":"10.1016\/j.bioorg.2020.103665"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e11171","DOI":"10.1016\/j.heliyon.2022.e11171","article-title":"P-glycoprotein and cancer: What do we currently know?","volume":"8","author":"Muriithi","year":"2022","journal-title":"Heliyon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e09777","DOI":"10.1016\/j.heliyon.2022.e09777","article-title":"P-glycoprotein: New insights into structure, physiological function, regulation and alterations in disease","volume":"8","year":"2022","journal-title":"Heliyon"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ejmech.2017.01.044","article-title":"Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells","volume":"128","author":"Paterna","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1111\/bph.15506","article-title":"BBIT20 inhibits homologous DNA repair with disruption of the BRCA1\u2013BARD1 interaction in breast and ovarian cancer","volume":"178","author":"Raimundo","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"112985","DOI":"10.1016\/j.ejmech.2020.112985","article-title":"Alkylated monoterpene indole alkaloid derivatives as potent P-glycoprotein inhibitors in resistant cancer cells","volume":"210","author":"Cardoso","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"113334","DOI":"10.1016\/j.ejmech.2021.113334","article-title":"Structural insights of oxindole based kinase inhibitors as anticancer agents: Recent advances","volume":"216","author":"Dhokne","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e202202361","DOI":"10.1002\/slct.202202361","article-title":"Indole Derived Anticancer Agents","volume":"7","author":"Mehra","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.ejmech.2014.06.056","article-title":"Spirooxindoles: Promising scaffolds for anticancer agents","volume":"97","author":"Yu","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2174\/09298673113206660325","article-title":"Targeting MDM2-p53 Interaction for Cancer Therapy: Are We There Yet?","volume":"21","author":"Nag","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1016\/j.bmcl.2015.05.015","article-title":"New indole\u2013isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies","volume":"25","author":"Panathur","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1128\/MCB.26.1.28-38.2006","article-title":"Inhibition of SIRT1 Catalytic Activity Increases p53 Acetylation but Does Not Alter Cell Survival following DNA Damage","volume":"26","author":"Solomon","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1021\/jm301448p","article-title":"Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design","volume":"56","author":"Friberg","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1002\/cmdc.201300291","article-title":"Sigma-2 Receptor Agonists as Possible Antitumor Agents in Resistant Tumors: Hints for Collateral Sensitivity","volume":"8","author":"Niso","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.cclet.2015.03.015","article-title":"Novel hybrids from N-hydroxyarylamide and indole ring through click chemistry as histone deacetylase inhibitors with potent antitumor activities","volume":"26","author":"Cai","year":"2015","journal-title":"Chin. Chem. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071414"}],"container-title":["Drugs and Drug Candidates"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2813-2998\/3\/3\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:19:33Z","timestamp":1760109573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2813-2998\/3\/3\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":90,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ddc3030029"],"URL":"https:\/\/doi.org\/10.3390\/ddc3030029","relation":{},"ISSN":["2813-2998"],"issn-type":[{"value":"2813-2998","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]}}}