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ISSN 2063-5346
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DESIGN, SYNTHESIS AND EVALUATION OF ANTITUBERCULAR, ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY OF NOVEL 1H-INDAZOLE DERIVATIVES

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Rajesh B. Nanaware, Anuruddha R. Chabukswar, Prajakta V. Adsule
» doi: 10.48047/ecb/2023.12.si8.486

Abstract

Despite decades of focused effort to eradicate it, TB still remains and is becoming more resistant to treatment. Due to the long duration of treatment for these diseases, their continual geographic spread, their rising level of drug resistance, as well as the toxicity and side effects connected with the currently available drugs, the development of novel antitubercular medications and regimens is necessary. In this study we are targeting the Indazole nucleus which offers wide substitution pattern on the ring and explored for the development of the newer efficient and safe molecules against tuberculosis, analgesia and inflammation. Here, some N-substituted indazoles were synthesized by using HATU as a coupling agent, which inhibits Enoyl acyl carrier protein reductase which is essential for the synthesis of mycolic acid in the tubercle bacilli. The molecular docking studies were found to be potentially binds to 2AQK enzyme. The results of the MD simulation showed that the test compound BOT was significantly stable in the Enoyl-ACP reductase-2AQK active site. The compound BOT-2AQK post-dynamic MM-GBSA analysis revealed substantial binding affinities with each of its chosen targets. Biological evaluation of synthesized compounds showed that, mycobacterium tuberculosis is effectively inhibited by the compound BDF, BOT, and BPM, while the compound BPT with the p-toluene group has the strongest analgesic and anti-inflammatory activity.

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