title: 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.
authors.affiliation: Department of Chemistry, University of Pune, Ganeshkhind Road, Pune 411007, India.
authors.forename: Dipti
authors.initials: D
authors.lastname: Shingnapurkar
authors.forename: Prasad
authors.initials: P
authors.lastname: Dandawate
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Anson
authors.forename: Annie K
authors.initials: AK
authors.lastname: Powell
authors.forename: Zahra
authors.initials: Z
authors.lastname: Afrasiabi
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Sinn
authors.forename: Shital
authors.initials: S
authors.lastname: Pandit
authors.forename: K
authors.initials: K
authors.lastname: Venkateswara Swamy
authors.forename: Scott
authors.initials: S
authors.lastname: Franzblau
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
mesh_terms: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents / Q000138:chemical synthesis*; D003300:Copper / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology; D011773:Pyruvates / Q000138:chemical synthesis*
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D011773:Pyruvates; D003300:Copper; D007522:Isocitrate Lyase; D007538:Isoniazid