Abstract
Three new series of 2-phenyl benzimidazole-based derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activity against breast cancer (MCF-7) cell lines. Three compounds 8, 9, and 15 showed high cytotoxic activities, with IC50 values of 3.37, 6.30, and 5.84μM, respectively, while they showed comparable cytotoxicity to the standard drug doxorubicin against human normal cells, including nontumorigenic breast epithelial cell line (MCF-10F), skin fibroblast cell line (BJ), and lung fibroblast cell line (MRC-5). Six of the synthesized compounds were screened against vascular endothelial growth factor receptor 2 (VEGFR-2) where compounds 8, 9, 12, and 15 exhibited an outstanding potency in comparison with sorafenib, with IC50 values of 6.7-8.9nM. Molecular docking study assessed the good binding patterns of the most potent compounds with the reported conserved amino acids of VEGFR-2 active site.
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