In vitro antiplasmodial activity, LC-MS analysis, and molecular docking studies of bioactive compounds from Tetrapleura tetraptera (Fabaceae) fruits
Date
2023
Authors
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Journal ISSN
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Publisher
Scientific African
Abstract
Malaria continues to be a major public health concern, particularly for children and pregnant
women in areas where the disease is endemic. Developing safe and efficient antimalarial therapies
to fight the disease is essential. Medicinal plants represent a potential source for the development
of new antimalarial drugs. Tetrapleura tetraptera is a plant native to West Africa and traditionally
used to treat several diseases including Malaria. Here, we investigated the antiplasmodial ac tivities of T. tetraptera fruit extracts against the chloroquine-sensitive (Pf3D7) and chloroquine resistant (PfDD2) strains of Plasmodium falciparum in vitro using SYBR green assay. In addition,
the antioxidant potential of the fruit extracts was also determined. LC-MS analysis was carried out
to identify the bioactive compounds in the extracts. Molecular docking studies provide significant
prima facie evidence of inhibition hence, to evaluate the potential inhibition of Plasmodium fal ciparum dihydroorotate dehydrogenase (PfDHODH), a validated malaria drug target, the identi fied compounds were docked against PfDHODH. Strong antiplasmodial activities were
demonstrated by the ethyl acetate and ethanolic extracts of T. tetraptera fruit, with IC50 values of
16.12 ± 0.04 µg/mL and 2.06 ± 0.02 µg/mL against the Pf3D7 strain, respectively. In the DPPH
radical scavenging experiment, the ethanolic extract revealed considerable antioxidant activity with an EC50 value of 0.21 ± 0.82 mg/mL. Seven bioactive compounds were identified in the
extract using LC-MS analysis. N-Methyl-1H-indole-3-propanamide (I), Tazolol (II), and Isopentyl
salicylate (III) were identified as potential inhibitors of PfDHODH with high binding affinities
ranging from -32.08 to -30.69 kcal/mol. The potential lead compounds also interacted with
Gly181, Leu531, and Arg265, which are critical amino acid residues in the catalytic activity of
PfDHODH. These findings support the traditional use of T. tetraptera fruit extracts for the treat ment of malaria and as promising avenues for antimalarial drug development.
Description
Research Article
Keywords
Antimalarial activity, Antioxidant, Malaria, Molecular docking, Dihydroorotate dehydrogenase