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

Bioorganic & medicinal chemistry letters 2012 Mar 16; In press

Shingnapurkar D, Dandawate P, Anson CE, Powell AK, Afrasiabi Z, Sinn E, Pandit S, Venkateswara Swamy K, Franzblau S, Padhye S

Department of Chemistry, University of Pune, Ganeshkhind Road, Pune 411007, India.

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.

Keywords: Isocitrate lyase tuberculosis