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Virtual screening of natural compounds for potential inhibitors of Sterol C‐24 methyltransferase of Leishmania donovani to overcome leishmaniasis
Author(s) -
Rahman Fazlur,
Tabrez Shams,
Ali Rahat,
Akand Sajjadul Kadir,
Zahid Mariya,
Alaidarous Mohammed A.,
Alsaweed Mohammed,
Alshehri Bader Mohammed,
Banawas Saeed,
Bin Dukhyil Abdul Aziz,
Rub Abdur
Publication year - 2021
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29944
Subject(s) - leishmania donovani , leishmaniasis , leishmania , ergosterol , druggability , biology , leishmania mexicana , biochemistry , chemistry , visceral leishmaniasis , parasite hosting , immunology , computer science , world wide web , gene
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 ( Ld SMT) 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 Ld SMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan‐3‐ol, and parthenolide showed the best binding affinity towards Ld SMT. 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.