Novel [(3-indolylmethylene)hydrazono]indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and <i>in vitro</i> biological evaluation

<p>On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (<b>6a–r</b>, <b>9a–f</b> and <b>11a–c</b>) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that <i>N</i>-propylindole derivatives were the most active compounds such as <b>6n</b> (MCF-7; IC₅₀=1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, <b>6n</b> increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds <b>6i</b>, <b>6j</b>, <b>6n</b> and <b>6q</b> generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7.