Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of new world tegumentary leishmaniasis.
Drug discovery
Epigenetics
Histone deacetylases inhibitors
Hydroxamic acid derivatives
Leishmania braziliensis
Tegumentary leishmaniasis
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
15
05
2020
revised:
01
08
2020
accepted:
03
08
2020
pubmed:
11
8
2020
medline:
1
1
2021
entrez:
11
8
2020
Statut:
ppublish
Résumé
The protozoan parasite Leishmania braziliensis is a major causative agent of the neglected tropical diseases Cutaneous and Mucocutaneous Leishmaniases in the New World. There are no vaccines to prevent the infection and the treatment relies on few drugs that often display high toxicity and costs. Thus, chemotherapeutic alternatives are required. Histone Deacetylases (HDACs) are epigenetic enzymes involved in the control of chromatin structure. In this work, we tested an in-house library of 78 hydroxamic acid derivatives as putative inhibitors of L. braziliensis HDACs (HDACi). The compounds were evaluated in relation to the toxicity to the host cell macrophage and to the leishmanicidal effect against L. braziliensis during in vitro infection. Eight HDACi showed significant leishmanicidal effects and the top 5 compounds showed effective concentrations (EC
Identifiants
pubmed: 32777278
pii: S0006-2952(20)30427-5
doi: 10.1016/j.bcp.2020.114191
pii:
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Nitric Oxide
31C4KY9ESH
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114191Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.