Kishor PALLEAPATI, Afzal Basha SHAIK, Venkataramana KALIKIVAYI

Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5- dihydro-1H-pyrazoles

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. TB is a global problem and is one of the major culprits responsible for the death of many in the developing world despite the availability of more than 20 drugs. Hence, there is an imperative need for the development of novel antitubercular drugs. To develop betteragents against tuberculosis, we synthesized a series of dihydropyrazole-1-carboxamides by the base-catalyzedcondensation of isoxazolyl chalcones with semicarbazide. The compounds were purified by column chromatography and characterized by spectral methods including IR, 1H NMR, 13C NMR and elemental analysis. The antitubercular activity was screened against Mycobacterium tuberculosis by MABA assay where isoniazid was used as positive control for comparing the activity. The studies revealed that isoxazole-1-carboxamides were more active compared to the corresponding chalcones. Substituents on the phenyl ring at position-5 of isoxazole ring played a crucial role in determining the antitubercular potency. The compounds 4n and 4o containing a blend of halogen and methoxyl groups at ortho and para positions of phenyl ring showed potency greater than the standard, isoniazid with MIC of 0.1 µg/mL and emerged as promising leads against TB. Further, 4n and 4o were assessed for their cytotoxic effects on L02 (human normal cell line) by using MTT assay. The compounds showed no cytotoxicity and established the safety of these compounds.

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WHO Global tuberculosis report 2017. http://www.who.int/mediacentre/news/releases/2017/politicalcommitment-tb/en/ (accessed on November 02, 2017).
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