O-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity
Autor: | Yudibeth Sixto-López, Margarita López-Viota, Sonia Panadero-Fajardo, Mavys Tabraue-Chávez, Mónica Díaz-Gavilán, José Pérez del Palacio, José Correa-Basurto, Joaquina Martín-Sánchez, Mercedes de la Cruz, Fernando Alves de Lima Franco, Nuria de Pedro, José F. Domínguez-Seglar, Victoriano Corpas-López, Francisco Franco-Montalban, Francisco Morillas-Márquez, Julian Lopez-Viota, José A. Gómez-Vidal |
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Rok vydání: | 2020 |
Předmět: |
chemistry.chemical_classification
0303 health sciences biology Chemistry Meglumine antimoniate Leishmania biology.organism_classification medicine.disease 01 natural sciences In vitro 0104 chemical sciences Amino acid 010404 medicinal & biomolecular chemistry 03 medical and health sciences Docking (dog) Biochemistry In vivo parasitic diseases Drug Discovery medicine Canine leishmaniasis Molecular Medicine Amastigote 030304 developmental biology medicine.drug |
Zdroj: | Journal of Medicinal Chemistry. 63:5734-5751 |
ISSN: | 1520-4804 0022-2623 |
Popis: | 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. |
Databáze: | OpenAIRE |
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