Novel 2,6-diketopiperazine-derived acetohydroxamic acids as promising anti-Trypanosoma brucei agents.
Future Med Chem
; 11(11): 1259-1266, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-31161793
ABSTRACT
Aim:
Identification of new, effective and selective trypanocidal agents. Materials &methods:
Twelve novel acetohydroxamic acid derivatives based on 2-alkyl-2-aryl-2,6-diketopiperazine scaffolds have been synthesized and evaluated in vitro for their growth inhibitory activity against bloodstream form Trypanosoma brucei.Results:
All the analogs were remarkably potent inhibitors, with low micromolar to submicromolar activities. Structure-activity relationship studies demonstrated that the presence of an alkyl substituent at the N(4)-position of the 2,6-diketopiperazine ring portion was, in general, beneficial to trypanocidal activity in this series.Conclusion:
The highest activity resulted from the introduction of a methyl, n-propyl or n-butyl substituent to the N(4)-position of the parent compound. Importantly, the most potent analogs were found to be highly selective against T. brucei with respect to mammalian cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
/
Trypanosoma brucei brucei
/
Dicetopiperazinas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2019
Tipo de documento:
Article