rifampin and actinonin

Topics: Amidohydrolases; Analysis of Variance; Animals; Antitubercular Agents; Colony Count, Microbial; Disease Models, Animal; Enzyme Inhibitors; Hydroxamic Acids; Isoniazid; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Rifampin; Tuberculosis

Bacterial peptide deformylase (PDF) catalyses removal of the N-terminal formyl group of proteins and is essential for protein maturation, growth and survival of bacteria. Thus, PDF appears to be a good antimycobacterial drug target. In the present study, various well-known PDF inhibitors, such as BB-3497, actinonin, 1,10-phenanthroline, hydroxylamine hydrochloride and galardin, were selected to evaluate their inhibitory activity against Mycobacterium tuberculosis. All compounds were found to be active against M. tuberculosis, with MIC(90) values (lowest drug concentration at which 90% of growth was inhibited on the basis of CFU enumeration) ranging from 0.2 mg/L to 74 mg/L. BB-3497 and 1,10-phenanthroline exhibited potent in vitro antimycobacterial activity, and also showed synergism with isoniazid and rifampicin. All compounds showed a bacteriostatic mode of inhibition. Under ex vivo conditions and short-course chemotherapy, BB-3497 and actinonin were found to be significantly active, with BB-3497 exhibiting comparable efficacy to that of isoniazid. Collectively, promising activities of PDF inhibitors such as BB-3497 and actinonin suggest their potential use against M. tuberculosis.

Topics: Amidohydrolases; Animals; Antibiotics, Antitubercular; Dipeptides; Drug Synergism; Drug Therapy, Combination; Hydroxamic Acids; Hydroxylamine; Isoniazid; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Phenanthrolines; Protease Inhibitors; Rifampin; Tuberculosis