In vitro effect of free and complexed indium(III) against Mycobacterium tuberculosis

In mycobacteria, the study of inhibition by metal ions has been limited by the absence of suitable molecular vectors. Recently, we reported on the inhibitory activity of a family of chelators, macrocyclic compounds (MCC), against Mycobacterium tuberculosis. In this study equimolar concentrations of the free cations vanadium(IV), arsenic(III), iron(III), indium(III) and bismuth(III), and as 1:1 complexes with the MCC 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetra-acetic acid (TETA) were tested in vitro against M. tuberculosis using the Bactec 460 TB radiometric technology (Becton-Dickinson, MD, USA). Radiometric inhibition above 80% was obtained with free indium(III) and bismuth(III), and ranged from 80% to 99%, with the complexes of TETA with vanadium(IV), bismuth(III) and indium(III), in the order of increasing activity. The highest radiometric inhibition levels were obtained with the [In(TETA)]- complex, which caused drops of up to 4 log units in cellular viability. The minimal inhibitory concentration of this compound was evaluated at 3 microM.