Leishmaniasis is a
neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania.
Leishmaniasis is transmitted from one human to other through the
bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region.
Sterol C-24
methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3-group from S-adenosyl
methionine to C-24 position of
sterol side chain which makes the
ergosterol different from
cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight
leishmaniasis.
Gigantol,
flavan-3-ol, and
parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction,
gigantol showed the best lead-likeness and drug-likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that
gigantol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes.
Gigantol exerted its antileishmanial action through the induction of
reactive oxygen species in dose-dependent manner. Our study, suggested the possible use of
gigantol as antileishmanial drug after further validations to overcome
leishmaniasis.