Synthesis and Antimycobacterial Activity of Symmetric Thiocarbohydrazone Derivatives against Mycobacterium bovis BCG

In this work, we reported the synthesis and evaluation of antimycobacterial and antifungalactivity of a series of thiocarbohydrazone derivatives which are thiacetazone congeners. Thetarget compounds were synthesized in superior yields by reacting thiocarbohydrazide withdifferent aromatic aldehydes and methyl ketones. Compounds 8, 19 and 25 were found to bethe most potent derivatives, exhibiting acceptable activity against Mycobacterium bovis BCGcompared to thiacetazone and ethambutol as reference substances. Compounds 8, 15 and 25exhibited the highest activity against Candida albicans. The most active compounds had acompletely different aromatic ring system with various electronic, steric and lipophilic natures.This is understandable in light of the fact that carbohydrazone derivatives must undergo ametabolic activation step before exerting their anti-TB activity and different SAR rules governeach one of these two processes.