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

Document Type: Research article

Authors

1 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 1- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Tehran, Pasteur Institute, 13164, Iran.

4 Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Tehran, Pasteur Institute, 13164

Abstract

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

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