Nano-carrier, design, synthesis, in silico ADMET, anti-proliferative assessments and docking of [1,2,4]triazolo[4,3-a]quinoxalines as Topo-II inhibitors and DNA intercalators.

Newly synthesized compounds 7, 8, and 9 and their nanogels as nano-carrier drug delivery systems have been synthesized and estimated for their cytotoxicity on MCF-7, HCT-116, HepG2, and A549. This research emphasizes on the formation and description of the Cs/PVA nanogel loaded with our derivatives 7, 8, and 9. The stability of nanogel formation was elucidated by zeta potential values which remained negative with values of -6.8, -11.8, and -7.8 mV respectively. The obtained compounds and their nanogels were evaluated as Topo-II inhibitors and DNA intercalators. The nanogel for compound 7 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 35.93%, 34.29%, 50.91%, and 49.94% respectively. Moreover, the nanogel for compound 8 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 31.13%, 34.09%, 49.59%, and 46.43% respectively. Furthermore, the nanogel for compound 9 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 38.99%, 43.78%, 58.25%, and 57.73% respectively. Moreover, our derivatives 7, 7 (nanogel), 8, 8 (nanogel), 9 and 9 (nanogel) exhibited high selectivity against cancer cells and lower toxicity on VERO cells with IC = 45.90-49.90 μM. Furthermore, the new derivatives demonstrated in silico very good anticipated ADMET profile. The nano-carrier formulations for the new derivatives may be purposeful as a prototype for future design, optimization, adaptation and investigation to obtain farther powerful selective anticancer agents.