O -Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity
( ) causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that -alkyl hydroxamate derivatives displayed potent and selective activity against the amastigote stage of while no activity was observed against promastigotes. Compound showed...
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Veröffentlicht in: | Journal of medicinal chemistry 2020-06, Vol.63 (11), p.5734-5751 |
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Hauptverfasser: | , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that
-alkyl hydroxamate derivatives displayed potent and selective
activity against the amastigote stage of
while no activity was observed against promastigotes. Compound
showed potent
activity against
. Moreover, the combination of compound
supported on gold nanoparticles and meglumine antimoniate was also effective
and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound
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
represents a new class of selective ligands with antileishmanial activity. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/acs.jmedchem.9b02016 |