Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum
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Date
2022-03
Journal Title
Journal ISSN
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Publisher
Elsevier
Abstract
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.
Description
Keywords
Gongronema latifolium Leaf, Pregnane glycosides, Antiplasmodial activity, Chloroquine resistance reversal
Citation
Adebayo, J. O., Ceravolo, I. P., Gyebi, G. A., Olorundare, O. E., Babatunde, A. S., Penna-Coutinho, J. P., Koketsu, M., & Krettli, A. U. (2022). Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum. Molecular and biochemical parasitology, 249, 111474.