Design, Synthesis, and Molecular Docking Studies of 5‐Bromoindole‐2‐Carboxylic Acid Hydrazone Derivatives: In Vitro Anticancer and VEGFR‐2 Inhibitory Effects

Abstract A new set of 5‐bromoindole‐2‐carboxylic acid hydrazone derivatives were synthesized and studied as potential inhibitors VEGFR‐2 tyrosine kinase (TK). Various physical (color, melting point, etc.) spectroscopic (IR, 1 H NMR, 13 C MS) methods used to determine the structure novel 5‐bromoindole derivatives. molecular docking study revealed that 5‐bromo‐N′‐(4‐hydroxy or 4‐chloro 4‐(dimethyl amino) benzylidene furan‐2‐ylmethylene)‐1 ‐indole‐2‐carbohydrazide had best binding energies against VEGFR TK domain. All newly compounds displayed adequate absorption levels did not appear inhibit cytochrome P450. Furthermore, they show in silico hepatotoxicity. The indole inhibited cell proliferation (measured by MTT assay) three human cancer lines tested, with 5‐bromo‐N′‐(4‐(dimethyl benzylidene)‐1 derivative (5BDBIC) being most potent Hep G2 hepatocellular carcinoma cells (IC 50 =14.3 μM), almost similar standard inhibitor sorafenib =6.2 μM). Compound 5BDBIC activity leading cycle arrest at G2/M phase, induction intrinsic apoptosis pathway. In conclusion, compound is a promising antitumor agent targets VEGFR.