Therapeutic potential of Stigmasterol and Kaempferol on multidrug-resistant malaria

Abstract

Falciparum malaria is the most common form of malaria in Nigeria and other countries where the disease is endemic. Increasing cases of multidrug-resistant falciparum malaria is a source of great concern in such areas. Plasmodium falciparum multidrug resistant 1 (pfmdr1) protein is an efflux pump that has been linked with drug resistance in malaria. Inhibiting pfmdr1 protein with novel drugs might provide a solution to malaria drug resistance. Considering the significance of this protein, this study aimed to model the protein structure and conduct molecular docking with stigmasterol and kaempferol as potential drug candidates. The three-dimensional structure of pfmdr1 was modeled in Phyre2 by homology modeling and validated through Volume Area Dihedral Angle Reporter (VADAR). The protein-drug interaction analysis of pfmdr1 protein and stigmasterol had an X-score of 6.857 kcal/mol, while the pfmdr1 protein-kaempferol complex had an X-score of 5.510 kcal/mol. As revealed by protein-ligand interaction profiling, stigmasterol formed hydrophobic interactions with Leu277, Leu281, Leu285, and His278 amino acid residues as compared to kaempferol, which formed similar interactions with only Ile282 and Leu285 residues. The results of this study suggest that stigmasterol and kaempferol are potential anti-malarial drugs, especially in areas of malaria drug resistance.