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New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2The Bcl-2 protein has been studied as an anticancer drug target in recent years, due to its gatekeeper role in resisting programmed cancer cell death (apoptosis), and the design of BH3 domain mimetics has led to the clinical approval of Venetoclax (ABT-199) for the treatment of chronic lymphocytic leukaemia. In this work we extend our previous studies on the discovery of indole-based heterocycles as Bcl-2 inhibitors, to the identification of quinolin-4-yl based oxadiazole and triazole analogues. Target compounds were readily synthesized via a common aryl-substituted quinolin-4-carbonyl-N-arylhydrazine-1-carbothioamide (5a⁻b) intermediate, through simple variation of the basic cyclisation conditions. Some of the quinoline-based oxadiazole analogues (e.g. compound 6i) were found to exhibit sub-micromolar anti-proliferative activity in Bcl-2-expressing cancer cell lines, and sub-micromolar IC50 activity within a Bcl2-Bim peptide ELISA assay. The Bcl-2 targeted anticancer activity of 6i was further rationalised via computational molecular modelling, offering possibilities to extend this work into the design of further potent and selective Bcl-2 inhibitory heteroaromatics with therapeutic potential.