New benzimidazole‐oxadiazole derivatives as potent VEGFR‐2 inhibitors: Synthesis, anticancer evaluation, and docking study

Abstract

AbstractWe report herein, the design and synthesis of benzimidazole‐oxadiazole derivatives as new inhibitors for vascular endothelial growth factor receptor‐2 (VEGFR‐2). The designed members were assessed for their in vitro anticancer activity against three cancer cell lines and two normal cell lines; A549, MCF‐7, PANC‐1, hTERT‐HPNE and CCD‐19Lu. Compounds 4c and 4d were found to be the most effective compounds against three cancer cell lines. Compounds 4c and 4d were then tested for their in vitro VEGFR‐2 inhibitory activity, safety profiles, and selectivity indices using the normal hTERT‐HPNE and CCD‐19Lu cell lines. It was determined that compound 4c was the most effective and safe member of the produced chemical family. Vascular endothelial growth factor A (VEGFA) immunolocalizations of compounds 4c and 4d were evaluated relative to control by VEGFA immunofluorescence staining. Compounds 4c and 4d inhibited VEGFR‐2 enzyme with half‐maximal inhibitory concentration values of 0.475 ± 0.021 and 0.618 ± 0.028 µM, respectively. Molecular docking of the target compounds was carried out in the active site of VEGFR‐2 (Protein Data Bank: 4ASD).