Dihydroeponemycin inhibits ubiquitin proteasome system of Plasmodium falciparum in silico

Abstract

Drug resistance in malaria treatment becomes major problems all over the world. Finding a novel potent antimalarial candidate is mandatory. Previous study proved that secondary metabolite of Streptomyces hygroscopicus Hygroscopicus containing eponemycin analog significantly inhibits Ubiquitin Proteasome System (UPS) of Plasmodium in vivo. The aims of this study are to know toxicity profile of dihydroeponemycin and its potency as Ubiquitin Proteasome System inhibitor of Plasmodium falciparum. The methods of this study were ADMET SAR Toxicity (ACD/LABS), Protein Modelling (SWISS), and Molecular Docking (AUTODOCK VINA PYRX). The result of Absorption, Distribution, Metabolism, Excretion and Toxicity profiles (ADMET) of dihydroeponemycin was absorbed 83.5% via intestinal route. Dihydroeponemycin belonged to Category 4 of toxicity. E3 is a potential drug target because of its different structure to that of the human. The C-score (confidence score of the prediction) of the active side E3 was 0.06 and E2 was 0.45. Dihydroeponemycin had the ability to bind to E3 and E2 with an affinity score binding of -3.8 and -4.1. The more negative the affinity binding value the easier the compound binds to the target protein. Based on this in silico study, dihydroeponemycin has potential effect as antimalaria by inhibiting Ubiquitin Proteasome System of Plasmodium falciparum.