Kazan Federal University Digital Repository

Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites

Show simple item record

dc.contributor.author Sidorov P.
dc.contributor.author Desta I.
dc.contributor.author Chessé M.
dc.contributor.author Horvath D.
dc.contributor.author Marcou G.
dc.contributor.author Varnek A.
dc.contributor.author Davioud-Charvet E.
dc.contributor.author Elhabiri M.
dc.date.accessioned 2018-09-19T21:50:23Z
dc.date.available 2018-09-19T21:50:23Z
dc.date.issued 2016
dc.identifier.issn 1860-7179
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/144404
dc.description.abstract © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim3-Benzylmenadiones are potent antimalarial agents that are thought to act through their 3-benzoylmenadione metabolites as redox cyclers of two essential targets: the NADPH-dependent glutathione reductases (GRs) of Plasmodium-parasitized erythrocytes and methemoglobin. Their physicochemical properties were characterized in a coupled assay using both targets and modeled with QSPR predictive tools built in house. The substitution pattern of the west/east aromatic parts that controls the oxidant character of the electrophore was highlighted and accurately predicted by QSPR models. The effects centered on the benz(o)yl chain, induced by drug bioactivation, markedly influenced the oxidant character of the reduced species through a large anodic shift of the redox potentials that correlated with the redox cycling of both targets in the coupled assay. Our approach demonstrates that the antimalarial activity of 3-benz(o)ylmenadiones results from a subtle interplay between bioactivation, fine-tuned redox properties, and interactions with crucial targets of P. falciparum. Plasmodione and its analogues give emphasis to redox polypharmacology, which constitutes an innovative approach to antimalarial therapy.
dc.relation.ispartofseries ChemMedChem
dc.subject chemoinformatics
dc.subject menadione
dc.subject multitarget drugs
dc.subject QSPR
dc.subject redox potential
dc.title Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites
dc.type Article
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 1339
dc.source.id SCOPUS18607179-2016-SID84976502436


Files in this item

This item appears in the following Collection(s)

  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics