Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-<i>a</i>:3',4'-<i>c</i>]quinoxaline derivatives as anticancer agents and apoptosis inducers

Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised were biologically investigated for their cytotoxic activities against HepG2 MCF-7. Also, the tested compounds further examined in vitro VEGFR-2 inhibitory activity. most promising derivative 23j was its apoptotic behaviour cell lines using flow cytometric western-plot analyses. Additional in-silico studies performed to predict how can bind determine drug-likeness profiling these derivatives. results revealed that 23a, 23i, 23j, 23l, 23n displayed highest antiproliferative two with IC50 values ranging from 6.4 19.4 µM. Furthermore, 23d, 23h, 23 m, showed 3.7 11.8 nM, comparing sorafenib (IC50 = 3.12 nM). Moreover, compound arrested growth at G2/M phase induced apoptosis by 40.12% compared control cells (7.07%). As well, such significant increase level caspase-3 (1.36-fold), caspase-9 (2.80-fold), BAX (1.65-fold), exhibited decrease Bcl-2 (2.63-fold).