In silico modeling revealed phytomolecules derived from Cymbopogon citratus (DC.) leaf extract as promising candidates for malaria therapy
Tekijät: Evbuomwan, Ikponmwosa Owen; Alejolowo, Omokolade Oluwaseyi; Elebiyo, Tobiloba Christiana; Nwonuma, Charles Obiora; Ojo, Oluwafemi Adeleke; Edosomwan, Evelyn Uwa; Chikwendu, Joy Ifeyinwa; Elosiuba, Nwanneka Victoria; Akulue, Justina Chimezie; Dogunro, Festus Ayorinde; Rotimi, Damilare Emmanuel; Osemwegie, Omorefosa Osarenkhoe; Ojo, Adebola Busola; Ademowo, Olusegun George; Adeyemi, Oluyomi Stephen; Oluba, Olarewaju Michael
Kustantaja: TAYLOR & FRANCIS INC
Kustannuspaikka: PHILADELPHIA
Julkaisuvuosi: 2024
Journal: Journal of Biomolecular Structure and Dynamics
Tietokannassa oleva lehden nimi: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Lehden akronyymi: J BIOMOL STRUCT DYN
Vuosikerta: 42
Numero: 1
Aloitussivu: 101
Lopetussivu: 118
Sivujen määrä: 18
ISSN: 0739-1102
eISSN: 1538-0254
DOI: https://doi.org/10.1080/07391102.2023.2192799
The emergence of varying levels of resistance to currently available antimalarial drugs significantly threatens global health. This factor heightens the urgency to explore bioactive compounds from natural products with a view to discovering and developing newer antimalarial drugs with novel mode of actions. Therefore, we evaluated the inhibitory effects of sixteen phytocompounds from Cymbopogon citratus leaf extract against Plasmodium falciparum drug targets such as P. falciparum circumsporozoite protein (PfCSP), P. falciparum merozoite surface protein 1 (PfMSP1) and P. falciparum erythrocyte membrane protein 1 (PfEMP1). In silico approaches including molecular docking, pharmacophore modeling and 3D-QSAR were adopted to analyze the inhibitory activity of the compounds under consideration. The molecular docking results indicated that a compound swertiajaponin from C. citratus exhibited a higher binding affinity (-7.8 kcal/mol) to PfMSP1 as against the standard artesunate-amodiaquine (-6.6 kcal/mol). Swertiajaponin also formed strong hydrogen bond interactions with LYS29, CYS30, TYR34, ASN52, GLY55 and CYS28 amino acid residues. In addition, quercetin another compound from C. citratus exhibited significant binding energies -6.8 and -8.3 kcal/mol with PfCSP and PfEMP1, respectively but slightly lower than the standard artemether-lumefantrine with binding energies of -7.4 kcal/mol against PfCSP and -8.7 kcal/mol against PfEMP1. Overall, the present study provides evidence that swertiajaponin and other phytomolecules from C. citratus have modulatory properties toward P. falciparum drug targets and thus may warrant further exploration in early drug discovery efforts against malaria. Furthermore, these findings lend credence to the folkloric use of C. citratus for malaria treatment.Communicated by Ramaswamy H. Sarma
