Synthesis and Characterization of Pyruvate-isoniazid Analogs and their Copper Complexes as Potential ICL Inhibitors
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.
D. Shingnapurkar and P. R. Dandawate and C. E. Anson and A. K. Powell and Z. Afrasiabi Navan and E. Sinn and S. Pandit and K. V. Swamy and S. G. Franzblau and S. B. Padhyé, "Synthesis and Characterization of Pyruvate-isoniazid Analogs and their Copper Complexes as Potential ICL Inhibitors," Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 9, pp. 3172-3176, Elsevier, May 2012.
The definitive version is available at http://dx.doi.org/10.1016/j.bmcl.2012.03.047
Keywords and Phrases
copper complex; enzyme inhibitor; glyoxylic acid; isocitrate lyase; isoniazid derivative; pyruvic acid; tuberculostatic agent; anaerobic metabolism; article; controlled study; drug conjugation; drug design; drug potency; drug structure; drug synthesis; enzyme inhibition; macrophage; Mycobacterium tuberculosis; nonhuman; Anti-Bacterial Agents; Antitubercular Agents; Copper; Enzyme Inhibitors; Humans; Isocitrate Lyase; Isoniazid; Mycobacterium tuberculosis; Pyruvates; Corynebacterineae; Mycobacterium tuberculosis; Copper complex; Isocitrate lyase; Persistent mycobacteria; Pyruvic acid
International Standard Serial Number (ISSN)
Article - Journal
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