<i>In vitro</i> and <i>in silico</i> analysis of <i>L. donovani</i> enoyl acyl carrier protein reductase - A possible drug target

The emergence of increased resistance to the available drugs has created a situation that demands to find out more specific molecular drug targets for Leishmaniasis. The enoyl acyl carrier protein reductase (ENR), a regulatory enzyme in type II fatty acid synthesis, was confirmed as a novel drug target and triclosan as its specific inhibitor in many microorganisms. In this study, the triclosan was tested for the leishmanicidal property against <i>Leishmania donovani</i> (<i>L. donovani</i>) and the results of <i>in vitro</i> and <i>ex vivo</i> drug assays on promastigotes and amastigotes showed that triclosan possessed antileishmanial activity with a half minimal inhibitory concentration (IC₅₀) of 30 µM. Consequently, adopting <i>in silico</i> approach, we have tested the triclosan’s ability to bind with the <i>L. donovani</i> enoyl acyl carrier protein reductase (<i>Ld</i>ENR). The 3D structure of <i>Ld</i>ENR was modelled, triclosan and cofactors were docked in <i>Ld</i>ENR model and molecular dynamic simulations were performed to observe the protein-ligands interactions, stability, compactness and binding energy calculation of the ligands-<i>Ld</i>ENR complexes. The observation showed that triclosan stably interacted with <i>Ld</i>ENR in presence of both the cofactors (NADPH and NADH), however, simulation results favor NADH as a preferred co-factor for <i>Ld</i>ENR. These results support that the reduction of <i>L. donovani</i> growth in the <i>in vitro</i> and <i>ex vivo</i> drug assays may be due to the interaction of triclosan with <i>Ld</i>ENR, which should be confirmed through enzymatic assays. The results of this study suggest that <i>Ld</i>ENR could be a potential drug target and triclosan as a lead for Leishmaniasis. Communicated by Ramaswamy H. Sarma