ReviewMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents2026
Indole-based derivatives as anticancer agents: recent advances in structure-activity relationships and biological mechanisms.
Review in Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Despite significant advances in cancer therapy, the clinical efficacy of many anticancer agents remains limited by poor selectivity, systemic toxicity, and the emergence of drug resistance, highlighting the need for novel therapeutic strategies. Among privileged heterocyclic scaffolds, indole has emerged as a versatile pharmacophore for the development of targeted anticancer agents owing to its structural diversity and broad biological activity. This review critically evaluates recent advances in indole-based anticancer agents, with particular emphasis on structure-activity relationships (SAR), molecular mechanisms, and target-oriented drug design. The discussion encompasses major therapeutic targets, including protein kinases (EGFR, VEGFR-2, CDKs, and Aurora kinases), tubulin, topoisomerases I and II, Bcl-2 family proteins, and histone deacetylases (HDACs). Comparative analysis identifies key SAR trends, successful optimization strategies, and the influence of structural modifications on potency, selectivity, and target specificity. The review further discusses current translational challenges, including pharmacokinetic limitations, toxicity, and resistance, while highlighting emerging approaches such as molecular hybridization, dual-target inhibitors, and rational scaffold optimization. Collectively, this review provides an integrated medicinal chemistry perspective that may facilitate the rational design and clinical translation of next-generation indole-based anticancer therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.