1,3,4-oxadiazoles with effective anti-mycobacterial activity.

Abstract

The search for new drugs to treat tuberculosis and nontuberculous mycobacteria (NTM)-caused diseases is still desired. This is the first study aimed at determining the activity of two innovative synthetic 1,3,4-oxadiazole molecules, (4-[cyclohexyl(ethyl) sulfamoyl]-N-[5-(furan-2-yl)-1,3,4-oxadiazol-2-yl]benzamide), namely LMM11, and ((N-cyclo-hexyl-N-ethylsulfamoil)-N-(5- (4-fluorophenyl)-1,3,4-oxadiazol-2-il) benzamide), namely LMM6, against Mycobacterium tuberculosis and nontuberculous mycobacteria, and their ability to present synergism in activity against M. tuberculosis when combined with anti-TB drugs. In vitro cytotoxicity studies were conducted in HeLa and VERO cells. The minimum inhibitory concentration (MIC) and combinatory effect were carried out in M. tuberculosis H37Rv and resistant isolates, NTM, and other genera of bacteria. The LMM6 and LMM11 MIC ranged from 8.27 to 33.07 µM and 15.58 to 70.30 µM in M. tuberculosis, respectively. LMM6 showed activity against M. smegmatis mc2 155 (8.25 μM), M. szulgai (2.05 μM), and M. kansasii (66.03 μM), while LMM11 showed activity against M. szulgai (8.77 μM), and M. smegmatis (70.19 μM). Synergism and modulatory activity of LMM6 and LMM11 with anti-TB drugs were observed, and they showed to be more selective for mycobacteria than HeLa and VERO cells. Both new oxadiazoles showed activity against mycobacteria, in fact, more pronounced against M. tuberculosis, and seem to bring light to the synthesis of new antimicobacterial.