Basic Information
ID: ALA4602729
Journal: J Med Chem
Title: O-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity.
Authors: Corpas-López V, Tabraue-Chávez M, Sixto-López Y, Panadero-Fajardo S, Alves de Lima Franco F, Domínguez-Seglar JF, Morillas-Márquez F, Franco-Montalbán F, Díaz-Gavilán M, Correa-Basurto J, López-Viota J, López-Viota M, Pérez Del Palacio J, de la Cruz M, de Pedro N, Martín-Sánchez J, Gómez-Vidal JA.
Abstract: Leishmania (L.) infantum causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that O-alkyl hydroxamate derivatives displayed potent and selective in vitro activity against the amastigote stage of L. infantum while no activity was observed against promastigotes. Compound 5 showed potent in vivo activity against L. infantum. Moreover, the combination of compound 5 supported on gold nanoparticles and meglumine antimoniate was also effective in vivo and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound 5 did not reach highly conserved pocket C and established interactions with the semiconserved residues V44, A45, R242, and E243 in pocket A of LiSIR2rp1. The surface space determined by these four amino acids is not conserved in human sirtuins. Compound 5 represents a new class of selective ligands with antileishmanial activity.
CiteXplore: 32392053
DOI: 10.1021/acs.jmedchem.9b02016
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets