Rambutan peel against drug resistance genes of Plasmodium falciparum and Plasmodium vivax isolated from the Philippines: An in silico analysis

Abstract

Malaria remains a critical health concern in the Philippines owing to the rising drug resistance of Plasmodium strains. The study aimed to investigate the antimalarial potential and efficacy of nine bioactive compounds derived from Nephelium lappaceum (Rambutan) peel against nine drug resistance genes of P. falciparum and P. vivax isolated from malaria-endemic areas in the Philippines. In silico approaches were employed encompassing homology modeling, molecular docking, and the assessment of physicochemical and pharmacokinetic properties, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). Among the nine examined phytochemicals, geraniin exhibited the strongest binding to putative proteins encoded by five drug resistance genes (pfmdr1, pfk13, pvmdr1, pvdhfr, and pvdhps), followed by corilagin (pfdhps and pvcrt-o), rutin (pfdhfr), and saponin (pfcrt). Hydrogen bonding, hydrophobic, and electrostatic interactions were identified as determinants of the binding stability. However, physicochemical properties revealed that corilagin, rutin, geraniin, and saponin violated four of Lipinski’s rules. ADMET analysis of the compounds revealed good water solubility, low absorption, and no hepatotoxicity; however, acute toxicity and poor bioavailability pose challenges for their development as antimalarial drugs. These findings demonstrate the antimalarial potential of the bioactive compounds from N. lappaceum peel; however, further in vivo and in vitro studies are recommended to validate their effects and efficacy.