Synthesis and characterization of pyruvate-isoniazid analogs and their copper complexes as potential ICL inhibitors

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• 作者：Dipti Shingnapurkar^a ; Prasad Dandawate^b ; Christopher E. Anson^c ; Annie K. Powell^c ; Zahra Afrasiabi^d ; Ekkehard Sinn^d ; Shital Pandit^f ; K. Venkateswara Swamy^f ; Scott Franzblau^e ; Subhash Padhye^a ; ^b ; ^{sbpadhye@hotmail.com} ; ^{sbpadhye@chem.unipune.ernet.in}
• 关键词：Pyruvic acid ; Isocitrate lyase ; Persistent mycobacteria ; Copper complex
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 May, 2012
• 年：2012
• 卷：22
• 期：9
• 页码：3172-3176
• 全文大小：665 K

文摘

Currently used anti-tubercular drugs target actively growing Mycobacterium tuberculosis (Mtb) but there are no current therapies targeting persistent mycobacteria. Isocitrate lyase (ICL) is an important enzyme of the glyoxylate shunt pathway used by Mtb for sustaining intracellular infection in inflammatory macrophages under conditions of stress such as nutrient depletion and anaerobic metabolism. Since the humans do not possess this enzyme it constitutes an attractive target for selective drug design. Present work describes synthesis and structural characterization of pyruvate-isoniazid conjugates and their copper complexes with potent anti-tubercular activities against M. tuberculosis H37Rv.