SAR-guided development of indole-matrine hybrids as potential anticancer agents via mitochondrial stress/cytochrome c/caspase 3 signaling pathway

•31 indole-matrine hybrids were developed by SAR-guided structural optimization strategy.•The most active hybrid 8g improved the anticancer activity of matrine by 3-orders of magnitude.•Intracellular click labelling of probe alkynyl-8g revealed a mitochondrial distribution for 8g.•8g strongly induced mitochondrial stress and activated cytochrome c/caspase 3 pathway.