Development of novel tetrahydrothieno[2,3-c]pyridine-3-carboxamide based Mycobacterium tuberculosis pantothenate synthetase inhibitors: Molecular hybridization from known antimycobacterial leads

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• 作者：Ganesh Samala ; Parthiban Brindha Devi ; Radhika Nallangi ; Jonnalagadda Padma Sridevi ; Shalini Saxena ; Perumal Yogeeswari ; Dharmarajan Sriram ; ^{dsriram@hyderabad.bits-pilani.ac.in" class="auth_mail}
• 关键词：Tuberculosis ; Pantothenate synthetase ; Cytotoxicity
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：15 March, 2014
• 年：2014
• 卷：22
• 期：6
• 页码：1938-1947
• 全文大小：1384 K

文摘

Twenty six 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide derivatives were designed by molecular hybridization approach using and synthesized from piperidin-4-one by five step synthesis. Compounds were evaluated for Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibition study, in vitro activities against MTB, cytotoxicity against RAW 264.7 cell line. Among the compounds, 6-(4-nitrophenylsulfonyl)-2-(5-nitrothiophene-2-carboxamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide (11) was found to be the most active compound with IC₅₀ of 5.87 卤 0.12 渭M against MTB PS, inhibited MTB with MIC of 9.28 渭M and it was non-cytotoxic at 50 渭M. The binding affinity of the most potent inhibitor 11 was further confirmed biophysically through differential scanning fluorimetry.