O-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity

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URI: https://hdl.handle.net/10481/107604
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Corpas-López, Victoriano; Tabraue-Chavez, Mavys; Sixto-López, Yudibeth; Panadero-Fajardo, Sonia; Alves de Lima Franco, Fernando; Domínguez Seglar, José Francisco; Morillas Márquez, Francisco; Franco Montalbán, Francisco; Díaz Gavilán, Mónica; Correa-Basurto, José; López-Viota, Julián; López-Viota Gallardo, Margarita; Pérez del Palacio, José; de la Cruz, Mercedes; de Pedro, Nuria; Martín Sánchez, Joaquina; Gómez Vidal, José Antonio
Editorial
American Chemical Society
Materia
Metal nanoparticles
 
Nanoparticles
 
Parasites
 
Peptides and proteins
 
Redox reactions
 
Date
2020-06-11
Sponsorship
This research was supported by Project P06-CTS-01407 from the Junta de Andalucía (Spain), Project GREIB.PT-2010-10 from the Universidad de Granada (Spain), and Project 20F12/7 from the Universidad de Granada (Spain).
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.
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