Expanding the occurrence of antimalarial metabolites in dorid nudibranch Hypselodoris tryoni

Abstract

This study examined the antimalarial activity of a furanosesquiterpene, furodysinin, one of the major metabolites of the dorid nudibranch Hypselodoris tryoni. The nudibranchs were collected from Balinese waters and the metabolites were purified by chromatography. Ex vivo rodent malaria Plasmodium berghei assays were conducted to determine the metabolite antimalarial activity. In silico molecular docking was employed to investigate the interaction between furodysinin against wild-type P. berghei and atovaquone-resistant P. berghei (Y268C). This study reported for the first time that the furodysinin displayed a promising antimalarial activity based on the ex vivo tests against wild-type P. berghei and atovaquone-resistant P. berghei. In silico molecular docking study showed that furodysinin inhibits the parasite mitochondrial cytochrome b (cyt b) by binding to the protein Qo pocket (ef-helix) where it interacts with residue 268, the mutation of which is known to confer resistance to atovaquone. Furodysinin binds to the mutated tyrosine at residue 268, which has changed to cysteine, forming an alkyl bond with C268 at a distance of 4.6 Å. Therefore, we predict that furodysinin has a target in Plasmodium mitochondria.