<i>In vitro</i> inhibition of <i>Mycobacterium tuberculosis β</i>-carbonic anhydrase 3 with Mono- and dithiocarbamates and evaluation of their toxicity using zebrafish developing embryos

Abstract

We investigated a panel of 14 compounds belonging to the monothiocarbamate (<b>MTC</b>) and dithiocarbamate (<b>DTC</b>) series against the β-carbonic anhydrase 3 (<i>β</i>-CA3) of <i>Mycobacterium tuberculosis</i> (Mtb). We also evaluated all compounds for toxicity using 1-5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective nanomolar or submicromolar <i>in vitro</i> inhibition against the <i>β</i>-CA3 (K_Is 2.4-812.0 nM), and among them four <b>DTCs</b> of the series (<b>8-10</b> and <b>12</b>) showed very significant inhibition potencies with K_Is between 2.4 and 43 nM. Out of 14 compounds screened for toxicity and safety 9 compounds showed no adverse phenotypic effects on the developing zebrafish larvae at five days of exposure. The results of <i>in vitro</i> inhibition and the toxicological evaluation of our study suggest that 5 compounds are suitable for further <i>in vivo</i> preclinical characterisation in zebrafish model.