Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of benzimidazole derivatives

Abstract

A series of benzimidazole derivatives (1–20) was synthesized and evaluated for its in vitro antimicrobial, antitubercular and anticancer activities. Compound 10 was found to be the most active antibacterial agent. The compounds active in in vitro evaluation against M. tuberculosis were further assessed for their in vivo activity in mice and for their capacity to inhibit the vital mycobacterial enzymes viz., isocitrate lyase, pantothenate synthetase and chorismate mutase. The dose of the compounds in antitubercular evaluation that proved fatal and highly toxic to mice was 5.67 mg/kg while lethal dose varied from 1.82 mg/kg to 3.23 mg/kg body weight of the mice. A dose of 1.34 mg/kg was found to be safe for each of the compounds. All compounds inhibited the mycobacterial enzymes but to a lesser extent than streptomycin sulphate used as positive control. Compound 19, exhibiting inhibition of 67.56%, 53.45%, and 47.56% against isocitrate lyase, pantothenate synthetase and chorismate mutase, respectively is the most potent antitubercular compound among the synthesized benzimidazole derivatives. Further, compound 19 also emerged as a potent anticancer agent (IC₅₀ = 0.0013 µM) than 5-flourouracil against breast cancer cell line (MCF 7).

Keywords:

• Microbial resistance
• MCF7 cell line
• Isocitrate lyase
• Pantothenate synthetase
• Chorismate mutase

Acknowledgement

This research work was supported by the Indian Council for Medical Research, New Delhi, India (Grant No. 45/14/2011/PHA/BMS).