Synthesis and Characterization of Pyruvate-isoniazid Analogs and their Copper Complexes as Potential ICL Inhibitors

Abstract

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.

Department(s)

Chemistry

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)

0960-894X

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2012 Elsevier, All rights reserved.

Publication Date

01 May 2012

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