In silicomodeling revealed phytomolecules derived from Cymbopogon citratus(DC.) leaf extract as promising candidates for malaria therapy

AbstractThe 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 citratusleaf extract against Plasmodium falciparumdrug targets such as P. falciparumcircumsporozoite protein (PfCSP), P. falciparummerozoite surface protein 1 (PfMSP1) and P. falciparumerythrocyte membrane protein 1 (PfEMP1). In silicoapproaches 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. citratusexhibited 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. citratusexhibited 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. citratushave modulatory properties toward P. falciparumdrug 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. citratusfor malaria treatment.Communicated by Ramaswamy H. Sarma