New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with in silico docking, ADMET, toxicity, and DFT studies.

ABSTRACT: A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC₅₀ ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC₅₀ = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were condu

SUBMITTER: Alanazi MM 

PROVIDER: S-EPMC9044819 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature