Isolation and evaluation of the enantiospecific antitubercular activity of a novel triazole compound

Sci Pharm. 2013 Oct 21;82(1):87-97. doi: 10.3797/scipharm.1308-15. Print 2014 Jan-Mar.


Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centers. To evaluate the enantiospecific antitubercular activity, the four stereoisomers were isolated using preparative chiral chromatography and the individual stereoisomers were evaluated using the resazurin microtiter assay method (REMA) and a microbroth dilution technique against the Mycobacterium tuberculosis H37Rv strain. Isomer III of MSDRT 12 was found to be the most potent with a minimum inhibitory concentration (MIC) of 0.78 μg/mL, Isomer II had a MIC of 12.5 μg/mL, and isomers I and IV showed no activity. The diastereomeric mixture of MSDRT 12 showed a MIC of 3.125 μg/mL and isoniazid, used as the standard drug, showed a MIC of 0.4 μg/mL. This confirms the necessity of screening individual enantiomers for their pharmacological activity early in the discovery phase to identify the most potent isomer for further development efforts.

Keywords: Antitubercular Compounds; Chiral Separation; Preparative Chiral Chromatography; REMA testing; Triazoles.