Rapid 'one-pot' synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents

Abstract

A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using sodium dithionite in dimethylsulfoxide. This 'one-pot' reaction was proceeded very smoothly, in short reaction time with an excellent yield. All the compounds (7a-r) were screened for their in vivo anti-inflammatory and in vitro antimicrobial activity. Most of the compounds exhibited remarkable paw-edema inhibition in the initial one hour of administration indicating the higher potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g displayed a high level of carrageenan-induced paw edema inhibition compared to that of indomethacin. Compound 7p exhibited very good antibacterial activity and antifungal activity with a MIC of 3.12 μg/mL against most of the tested organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors of Aspergillus niger with MIC of 3.12 μg/mL. Cytotoxicity of the potent compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and are found to be non toxic at the highest concentration used (i.e., 10 μg/mL).

Keywords: Anti-inflammatory activity; Antimicrobial activity; Hydrazones; Reductive cyclization; ‘One-pot’ method.