Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum.

Autor: Adebayo JO; Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria. Electronic address: topebayo2002@yahoo.com., Ceravolo IP; Instituto René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil., Gyebi GA; Department of Biochemistry, Faculty of Science and Technology, Bingham University, Karu, Nasarawa, Nigeria., Olorundare OE; Department of Pharmacology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria., Babatunde AS; Department of Haematology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria., Penna-Coutinho JP; Instituto René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil., Koketsu M; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Gifu, Japan., Krettli AU; Instituto René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil.
Jazyk: angličtina
Zdroj: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2022 May; Vol. 249, pp. 111474. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1016/j.molbiopara.2022.111474
Abstrakt: The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3-4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 µg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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