Rational design, synthesis, and anti-cancer evaluation of amide derivatives of 1,3,4-Thiadiazole benzimidazoles

Abstract

A series of amide derivatives of 1,3,4-thiadiazole-benzimidazole (13a-j) has been designed, synthesized and screened for their anticancer activities against human breast cancer cell line (MCF-7), human lung cancer (A549), human colon cancer (Colo-205) & human ovarian cancer (A2780) by employing of MTT method with Etoposide as standard drug. Among the synthesized derivatives, the compound 13a with electron donating 3,4,5-trimethoxy substituent showed potent anticancer activity (MCF-7 = 0.04 ± 0.008 µM; A549 = 0.06 ± 0.009 µM; Colo-205 = 0.12 ± 0.067 µM & A2780 = 0.19 ± 0.071 µM. The compound 13a, shown two H-bonding contacts with PHE106, TYR 67 amino acids are O and NH group, as well as with additional hydrophobic interactions, including − stacking with aromatic rings and also had a binding affinity of −12.04 kcal/mole.

Keywords

• Nocodazole
• Benzimidazole
• Azepeta
• 1,3,4-thiadiazole
• Anticancer activity