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

Abstract

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

Keywords:

• Cymbopogon citratus
• malaria
• swertiajaponin
• PfMSP1
• molecular docking

Authors’ contributions

IOE, OOA, TCE, CON, OAO, EUE, OGA, OSA, and OMO designed the study. IOE, OOA, TCE, DER, OSA, and OMO carry out the study. IOE, OAO, JIC, NVE, JCA, FAD, DER, OOO, ABO, OSA, and OMO evaluated and interpreted the data. IOE, OAO, EUE, OOO, OSA, and OMO prepared the draft manuscript. IOE, OAO, OGA, OSA, and OMO finalized the manuscript. All authors approved the final version of the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by research funding from the Royal Society for Tropical Medicine and Hygiene (Grant No. 0021462). The funding body had no role whatsoever in the study design, data collection and analysis, manuscript preparation, and decision to publish.