Antimicrobial activities of substituted 4-N-alkylated-2-trifluoromethylquinoline analogs against nontuberculous mycobacteria

Abstract

Background: Many contagious diseases have been caused by a variety of nontuberculous mycobacteria, opportunistic pathogens that can cause disseminated or localized diseases, particularly pulmonary, skin, and soft tissue infections. Objective: In this study fifty five substituted 4-N-alkylated-2-trifluoromethylquinoline were evaluated against five species of nontuberculous mycobacteria: Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium abscessus, Mycobacterium kansasii, and Mycobacterium avium. Methods: The antimycobacterial activities of all tested compounds were assessed using the microplate procedure with broth microdilution assay. The most actives were selected for their potential cytotoxic activity against Vero cells. Results: Most of the compounds displayed some activity against M. kansaii, of which 12, 15, 34, 37 and 48 were the most active at 3.12 g/mL. The derivative 8 was the most active against M. fortuitum at 6.25 g/mL and the most active against M. chelonae at 3.12 g/mL. The derivative 2 was the most active against M. avium at 12.5 g/mL, and 9 the most active against M. abscessus at 12.5 g/mL. All the most active compounds showed MIC values similar to the references drugs used against these species. Conclusion: 47 compounds displayed some activity against some of the species analyzed, highlighting derivatives 12, 15, 34, 37, and 48, which presented the lower MIC values. Compounds 34 and 37 displayed the highest activity and not showed cytotoxicity against Vero cells. These findings open new perspectives for the research of new drugs against these mycobacterial species based on the quinoline nucleus.