Isoxazole Clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles: Design, Synthesis, Characterization and Antitubercular Evaluation

Abstract

Tuberculosis (TB) is a global problem inspite the availability of drugs. This state of affairs is due to the limitations of existing drugs including muti-drug resistance and toxicites. As a result, there is a pressing need for new antitubercular medicines to be developed. In the present investigation we designed and synthesized a series of isoxazole clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles (16-30) in considerable yeilds (43-78%). Further these compounds were purified by recrystallization and charcterized by spectral techniques-Mass, FT-IR and 1H NMR and then evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Among the tested compounds, the analogues 24 bearing 3,5-dimethoxyphenyl scaffold at the 5th position of 4,5-dihydro-1H-pyrazole ring showed superior activity than isoniazid (MIC = 0.25 µg/mL) with MIC value 0.1 µg/mL whereas the compound 25 containing 2,3,4-trimethoxyphenyl had equal potency as that of isoniazid. Additionally, 24 and 25 were found to be less selective towards the human normal liver cell lines-LO2 in their cytotoxicity assays. Hence, these two compounds are safe and useful lead candidates for the development of novel antitubercular drugs.