Microwave synthesis, biological evaluation and docking studies of 2-substituted methyl 1-(4-fluorophenyl)-1H-benzimidazole-5-carboxylates

A library of 22 novel 2-substituted fluorinated benzimidazoles ( 5a-v ) was synthesized under microwave conditions in yields of between 85–96% and tested for their antimicrobial and antioxidant activity. Two trioxygenated derivatives 5p and 5r had minimum bactericidal concentration values ranging between 14.5–115.7 μM ( 5p ) and 25.6–74.3 μM ( 5r ) against S. aureus , E. coli , P. aeruginosa and K. pneumoniae . The benzimidazole 5e with a CF 3 substituent had the best antifungal activity at 94.3 µM against C. albicans . Compounds 5p and 5r also showed good antioxidant activities of 386.6 and 306.7 µM respectively, comparable to that of ascorbic acid. Docking studies of 5 h and 5r into the active site of topoisomerase II DNA-gyrase indicated that interaction with the Mn 2+ ion in the active site of the enzyme was crucial for antibacterial activity.