Background: With approximately one-third of the world’s population infected, tuberculosis
continues to be a global public health crisis. The rise of strains that are unusually virulent or
highly resistant to current drugs is a cause of special concern, prompting research into new classes
of compounds, as well as the re-evaluation of known chemotherapeutic agents.
Objectives: The antimycobacterial activities associated with some recently-reported thiocarbonyl
compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and
carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug
design and discovery.
Methods: In the present study, the title compounds 3 and 4 were prepared by the condensation of
hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and
solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc
diffusion, and minimum inhibitory concentrations were determined against the virulent strain M.
Results: The chemical structures of these thermally stable compounds were determined by IR, 1HNMR,
13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc
diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In
some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates.
Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound
3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 μg/mL.
Conclusion: We found that the title compounds may be prepared conveniently in excellent purity
and good yields. They are readily identified on the basis of their characteristic spectra. Some members
of this class showed significant activities against mycobacteria. We conclude that further work
will be warranted in exploring the antitubercular properties of these compounds.
Keywords: Tuberculosis, Hydrazinecarbothioamide, Carbonothioic dihydrazide, Thiourea, Antitubercular, Kirby-Bauer, Isoxyl, Thiacetazone.
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