SYNTHESIS AND CHARACTERIZATION OF NEW DERIVATIVES OF PYRAZOLE AND SCREENED FOR THEIR ANTITUBERCULAR POTENTIAL

Objective: The objective of the paper was to synthesize and characterize new derivatives of thiazole-based pyrazole derivatives and evaluate them for the antitubercular activity.

Material and methods: The pyrazole derivatives have been synthesized by the two steps process in that first step pyrazole based carbothioamide compounds was synthesized and it further reacted with 3-(2-bromoacetyl)-2H-chromen-2-one to from the final compounds. Total Fourteen compounds have been synthesized and characterized by IR, ¹HNMR, elemental analysis and mass spectral analysis. The final Compounds (TP-1 to TP-14) have been evaluated for antitubercular activity by two Ex-vivo method i.e. LRP assay and MABA method.

Result and Discussion: IR analysis of compound TP-1 to TP-14 showed the occurrence of the characteristics peak at 3415-3420 (-NH), 1717-1721 (-C=O) and 1627 (-C=N). The 1H-NMR spectrum shown a singlet peak at δ 8.53, due to the chromen-2-one-4H proton. The characteristic peak of -NH proton was attributed at δ 12.02-12.03.  The MABA method depicted the efficacy of compound by MIC value in µg/ml; five compounds i.e. TP-8 (1.75), TP-3 (1.75), TP-9 (2.50), TP-10 (2.25), and TP-1 (2.25) have shown lowest MIC among all other compounds and it was similarly active with the standard anti-TB drug Isoniazid (MIC value 1.25 µg/ml). Luciferase reporter phase assay result data suggested that at 100µg/ml concentration, 10 compounds (TP-1, TP-2, TP-3, TP-4, TP-5, TP-8, TP-9, TP-10 TP-11 and TP-12) shown the potent anti-tubercular activity. Structure activity relationship (SAR) of the compound indicated that 4-chlorophenyl substitution at 3^rd position of pyrazole with 4-chlorophenyl, 4-nitrophenyl and 4-methylphenyl substitution at 1^st position of pyrazole have enhance the anti-tubercular potential.

Keywords: Anti-tubercular activity, LRP assay, MABA method, pyrazole, Thiazole