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.
Subject(s)
Antitubercular Agents/chemical synthesis , Copper/chemistry , Isocitrate Lyase/antagonists & inhibitors , Isoniazid/analogs & derivatives , Pyruvates/chemical synthesis , Anti-Bacterial Agents , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Humans , Isoniazid/chemical synthesis , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/enzymologyABSTRACT
Schiff base conjugates of p-aminosalicylic acid have been synthesized and characterized by elemental analysis, IR and (1)H NMR spectroscopy and cyclic voltammetry. Compounds containing hydroxyl-rich side chains show enhanced antimycobacterial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG. Higher ClogP values and superior radical scavenging activities are thought to be the contributing factors for their enhanced antimycobacterial activities.
