@Article{biocell.2021.016682,
AUTHOR = {FAZLUR RAHMAN, SHAMS TABREZ, RAHAT ALI, SAJJADUL KADIR AKAND, MOHAMMED A. ALAIDAROUS, MOHAMMED ALSAWEED, BADER MOHAMMED ALSHEHRI, SAEED BANAWAS, ABDUR RUB, ABDUL AZIZ BIN DUKHYIL},
TITLE = {Identification of potential inhibitors for Sterol C-24 reductase of <i>Leishmania donovani</i> through virtual screening of natural compounds},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {6},
PAGES = {1601--1610},
URL = {http://www.techscience.com/biocell/v45n6/44280},
ISSN = {1667-5746},
ABSTRACT = {Leishmaniasis is a vector-borne parasitic neglected tropical disease caused by a group of about 30 different
species of the genus <i>Leishmania</i>. 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 <i>Leishmania donovani</i>, 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 <i>LdSR</i> to identify a potential inhibitor to
fight leishmaniasis. Capsaicin, prenyletin, flavan-3-ol, resveratrol, and gingerol showed the top binding affinity towards
<i>LdSR</i>. 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 <i>LdSR</i>.},
DOI = {10.32604/biocell.2021.016682}
}