Design, synthesis and molecular docking of novel 4-morpholino-1H-pyrrolo[2,3-b] pyridine-5-carboxamides and 4-methylpiperazin-1H-pyrrolo[2,3-b] pyridine-5-carboxamides for the evaluation anti-cancer activity

Abstract

A novel series of 4-morpholino-1H-pyrrolo[2,3-b] pyridine-5-carboxamides (6 a-j) and 4-methylpiperazin-1H-pyrrolo[2,3-b] pyridine-5-carboxamides (9 a-i) have been designed and synthesized. All the synthesized compounds were well characterized and screened for their anti-cancer activity against MCF-7 breast cancer cell lines and A549 Lung cancer cell lines. The result of this study discloses that the synthesized compounds were shown good to moderate activity. The IC50 values of the tested compounds against MCF-7 cell lines are ranged from 16-111.9µg/mL. Whereas the IC50 values of the tested compounds against A-549 cancer cell line are ranged from 21-115.3 µg/mL. Among, the synthesized compounds, 6h exhibited significant cytotoxic activity against MCF-7 and A-549 with IC50 16µg/mL and 21µg/mL respectively. Based on the in vitro cytotoxic activity results, compound 6h and 9i showed good activity. Molecular docking experiments were conducted for 6h and 9i with EGFR (PDB ID-4HJO). Among these two, 6h has exhibited the highest binding energy (-11.22 kcal/mol) and 9i has exhibited remarkable binding energy (-8.06 kcal/mol).