Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 mu M and 15.21 mu M against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.

Automated summary

In this study, a series of novel benzoxazole derivatives were designed, synthesized, and evaluated for their potential as VEGFR-2 inhibitors. Compound 12l showed high growth inhibitory activity against HepG2 and MCF-7 cell lines and demonstrated promising VEGFR-2 inhibitory activity. Further investigation revealed that 12l could arrest cell growth at the Pre-G1 and G1 phases, induce apoptosis, and regulate key proteins involved in apoptosis. Docking studies suggested that 12l interacted with key amino acids similar to sorafenib.