Synthesis, characterisation and antitubercular activities of a series of pyruvate-containing aroylhydrazones and their Cu-complexes

Abstract

A series of eight pyruvate-based aroylhydrazones was synthesised and characterised. The reaction of the sodium salts of the aroylhydrazones with one equivalent of copper(ii) chloride allowed the isolation of neutral 1:1 complexes in which the hydrazones occupy three basal coordination sites of a square pyramidal Cu(ii)-centre, with two solvent molecules completing the coordination sphere. Structural details were obtained through the determination of the crystal structures of two representative pyruvate-based aroylhydrazones and three Cu(ii) complexes. The evaluation of the antimycobacterial activity of the sodium salts of the eight pryruvate hydrazones showed that the compounds are essentially inactive in their anionic form. The corresponding neutral Cu(ii) complexes, however, exhibit promising antimycobacterial activities if tested under high iron (8 μg Fe per mL) conditions. As observed for the related antimycobacterial agent isoniazid, the activity of the complexes decreases if the M. tuberculosis cells are grown under low iron (0.02 μg Fe per mL) conditions. The Cu(ii) complexes may thus have a similar mode of action and may require an iron-containing heme-dependent peroxidase for activation. © 2012 The Royal Society of Chemistry.