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

作　　者：FAZLUR RAHMAN SHAMS TABREZ RAHAT ALI SAJJADUL KADIR AKAND MOHAMMED AALAIDAROUS MOHAMMED ALSAWEED BADER MOHAMMED ALSHEHRI SAEED BANAWAS ABDUR RUB ABDUL AZIZ BIN DUKHYIL 

机构地区：[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

出　　处：《BIOCELL》2021年第6期1601-1610,共10页生物细胞（英文）

基　　金：Deanship of Scientific Research at Majmaah University,Al Majmaah,11952,Saudi Arabia for supporting this work under the Group Project No.RGP-2019-31.

摘　　要：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.

关 键 词：LEISHMANIA GINGEROL Sterol C-24 reductase Molecular docking ROS 

分 类 号：R73[医药卫生—肿瘤]