Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Autor: Rahman F; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India., Tabrez S; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India., Ali R; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India., Akand SK; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India., Zahid M; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India., Alaidarous MA; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia.; Department of Vice Rector for Graduate Studies and Scientific Research, Health and Basic Sciences Research Center, Majmaah University, Al Majmaah, Saudi Arabia., Alsaweed M; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia., Alshehri BM; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia., Banawas S; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia.; Department of Vice Rector for Graduate Studies and Scientific Research, Health and Basic Sciences Research Center, Majmaah University, Al Majmaah, Saudi Arabia., Bin Dukhyil AA; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia., Rub A; Department of Biotechnology, Infection and Immunity Lab (414), Jamia Millia Islamia (A Central University), New Delhi, India.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2021 May 06. Date of Electronic Publication: 2021 May 06.
DOI: 10.1002/jcb.29944
Abstrakt: 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.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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