Synthesis of aminophenylhydroxamate and aminobenzylhydroxamate derivatives and in vitro screening for antiparasitic and histone deacetylase inhibitory activity.
Int J Parasitol Drugs Drug Resist
; 8(1): 59-66, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29414107
ABSTRACT
A series of aminophenylhydroxamates and aminobenzylhydroxamates were synthesized and screened for their antiparasitic activity against Leishmania, Trypanosoma, and Toxoplasma. Their anti-histone deacetylase (HDAC) potency was determined. Moderate to no antileishmanial or antitrypanosomal activity was found (IC50â¯>â¯10⯵M) that contrast with the highly efficient anti-Toxoplasma activity (IC50â¯<â¯1.0⯵M) of these compounds. The antiparasitic activity of the synthetized compounds correlates well with their HDAC inhibitory activity. The best-performing compound (named 363) express a high anti-HDAC6 inhibitory activity (IC50 of 0.045⯱â¯0.015⯵M) a moderate cytotoxicity and a high anti-Toxoplasma activity in the range of known anti-Toxoplasma compounds (IC50 of 0.35-2.25⯵M). The calculated selectivity index (10-300 using different human cell lines) of the compound 363 makes it a lead compound for the future development of anti-Toxoplasma molecules.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Histona Desacetilases
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Histona Desacetilases
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Ácidos Hidroxâmicos
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Antiparasitários
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article