N-Mannich bases of benzimidazole as a potent antitubercular and antiprotozoal agents: Their synthesis and computational studies

Abstract

This article dealing with the microwave assisted synthesis of N-Mannich bases of pyridine clubbed with two different benzimidazole cores with their micromolar biological potency. All the synthesized compounds were evaluated for their in-vitro antibacterial, antimycobacterial and antiprotozoal potency. One of the final compound was found to be most active against M. tuberculosis (MIC = 3.125 µM) in the primary screening. N-Mannich bases of benzimidazole with pyridine-3-amine and 5-methyl-pyridine-2-amine showed potency against L. mexicana and T. cruzi respectively with IC50 value 0.25 and 1.02 µg/mL. Compound 4a showed good binding energy in the active pocket of receptor (PDB: 4cod) with −11.013 docking score. The stability of docked complex was validated by performing Molecular dynamics (MD) up to 20 ns simulation time. In silico ADME parameters and toxicity predicted that the active compounds belong to the Class IV GHS with LD50 value 1360 mg/kg and hence found to be mildly toxic.