<i>Eleutherine plicata</i> Herb. and Its Promising Constituents Amoebicides.

Abstract

<i>Eleutherine plicata</i> is used in the Amazon region for the treatment of amoebiasis. The plant has been found to contain naphthoquinones (eleutherin and isoeleutherin) and naphthalene derivatives (eleutherol and isoeleutherol), which have been isolated. This study investigated, through molecular docking, the potential of isoeleutherin, eleutherin, eleutherol, and isoeleutherol against different proteins of <i>Entamoeba histolytica</i>. The potential amoebicidal effects were assessed by examining the interaction with two proteins, O-acetyl-serine sulfhydrylase (3BM5) and thioredoxin reductase (4CCQ), obtained from the public RCSB PDB database. The proteins were optimized using the APBS server, which added charges, polar hydrogens, water molecules, and cocrystallized components. The enzymes were subsequently removed. In this study, the amoebicidal potential of the molecules isoeleutherin, eleutherin, isoeleutherol, and eleutherol was evaluated. In <i>in silico</i> studies, in MM/GBSA energy calculations, isoeleuterin was the most promising ligand (-27.67 kcal/mol) in the EhTrxR target, while in the EhOASS target, it maintained a competitive binding energy (-20.30 kcal/mol), being the most promising natural compound. In addition, it has a lower toxicity profile. The search for therapeutic alternatives for the treatment of amoebiasis is important, with <i>in silico</i> studies being one strategy. Isoeleuterin is the most promising molecule for <i>in vitro</i> and <i>in vivo</i> validation studies.