Synthesis of benzothiazolopyrazoloisonicotinohydrazide derivatives and their nitro regioisomers for antitubercular activity

Abstract

The history of incessant struggle and the current global burden associated with emerging infectious disease especially tuberculosis, guided us to define the scope of this research project, and to identify research gaps in synthesizing some heterocyclic compounds for anti-tubercular activity. In this research project, we have synthesized a series of novel heterocyclic (benzothiazoles) compounds viz N'-((1-(7-chloro-6-fluorobenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazol-4-yl)
methylene)isonicotinohydrazide 12a-c their 5-nitro 15a-c and 4-nitro 18a-c derivatives, by a series of reactions of their respective synthons. The completion of reaction and the purity of the synthesized compounds have been established by chromatographic analysis. All the newly synthesized compounds satisfactorily show acceptable analysis for their anticipated structures, which have been confirmed based on physicochemical and spectral data. These newly synthesized compounds have been primarily evaluated for their in vitro anti-tubercular activity by Ziehl-Neelsen stain method. Compounds 15a, 15b, 15c, 18b and 18c have shown 100% inhibition at 25 mg/ mL and MIC values of around 45 nM against M. tuberculosis H₃₇Rv (ATCC 27294). Cytotoxicity on THP-1 cell line shows that all the tested compounds are safe.