Open Access

ARTICLE

Identification of potential inhibitors for Sterol C-24 reductase of Leishmania donovani through virtual screening of natural compounds

FAZLUR RAHMAN^1,#, SHAMS TABREZ^1,#, RAHAT ALI¹, SAJJADUL KADIR AKAND¹, MOHAMMED A. ALAIDAROUS^2,3, MOHAMMED ALSAWEED², BADER MOHAMMED ALSHEHRI², SAEED BANAWAS^2,3, ABDUR RUB^1,*, ABDUL AZIZ BIN DUKHYIL^2,*

1 Infection and Immunity Laboratory (414), Department of Biotechnology, Jamia Millia Islamia-A Central University, New Delhi, 110025, India
2 Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, 11952, Saudi Arabia
3 Health and Basic Sciences Research Center, Majmaah University, Al Majmaah, 11952, Saudi Arabia

* Corresponding Authors: Abdur Rub, ; Abdul Aziz Bin Dukhyil,
# These authors contributed equally to this work

BIOCELL 2021, 45(6), 1601-1610. https://doi.org/10.32604/biocell.2021.016682

Received 17 March 2021; Accepted 25 April 2021; Issue published 01 September 2021

Abstract

Leishmaniasis is a vector-borne parasitic neglected tropical disease caused by a group of about 30 different species of the genus Leishmania. It is transmitted by the bite of female phlebotomies sand fly. Three main clinical manifestations of leishmaniasis include cutaneous, visceral, and mucocutaneous leishmaniasis. Visceral leishmaniasis (VL) caused by Leishmania donovani, is an infection of reticuloendothelial system and fatal if untreated. Cholesterol, a sterol that is prominent in the mammalian cell membranes whereas stigmasterol and ergosterol are more prevalent in plants, yeast, and protozoa, respectively. Ergosterols which is absent in human being, is an important constituent of parasite membrane. Sterol C-24 reductase (LdSR) enzyme catalyzes the final step in the ergosterol biosynthesis pathway. The inhibition of biosynthesis of ergosterol may lead to decreased cell viability and growth. Here, we performed the molecular docking-based virtual screening of a library of natural ligands against LdSR to identify a potential inhibitor to fight leishmaniasis. Capsaicin, prenyletin, flavan-3-ol, resveratrol, and gingerol showed the top binding affinity towards LdSR. Based upon ADME properties and bioactivity score, gingerol showed the best lead-likeness and drug-likeness properties. Hence, we further annotated its leishmanicidal properties. We found that gingerol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes. Gingerol exerted its antileishmanial action through the induction of reactive oxygen species (ROS) in concentration-dependent manner. Gingerol induced ROS led to apoptosis. Overall, this study described that gingerol would act as possible inhibitor to LdSR.

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