Recent advances in quinoline-based hybrid anticancer agents (2025-present): Synthetic strategies, SAR and mechanistic...

This review highlights the recent emerging therapeutic potential of quinoline-based scaffolds in anticancer drug discovery. A systematic and integrative review methodology was adopted, emphasising recent literature on synthetic strategies, structure-activity relationship (SAR) trends, mechanistic insights and in vitro/in vivo evaluations of quinoline derivatives. Modern synthetic approaches have enabled the efficient construction of structurally diverse quinoline hybrids with enhanced pharmacological profiles. Biological investigations reveal that several quinoline hybrids exhibit potent anticancer activity in low micromolar to submicromolar ranges. Additionally, exceeding the efficacy of standard drugs while demonstrating enhanced selectivity towards cancer cells. Mechanistically, these compounds act through multi-target modulation, induction of apoptosis, mitochondrial dysfunction and cell cycle arrest. SAR analyses indicated that strategic substitutions on the quinoline core and hybridisation with bioactive compounds enhance target binding and efficacy. Furthermore, in silico approaches, including molecular docking and ADME profiling, provide critical support for experimental findings and facilitate rational lead optimisation. Despite promising outcomes, challenges related to drug resistance, toxicity and pharmacokinetics persist. These limitations may be addressed through continuous advancement in the design and optimisation of anticancer-active molecular frameworks. Overall, quinoline hybrids represent a versatile and promising scaffold for the development of next-generation anticancer agents.