Optimization of the electrophile of chloronitrobenzamide leads active against Trypanosoma brucei.
Bioorg Med Chem Lett
; 23(14): 4127-31, 2013 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-23746473
ABSTRACT
We previously reported the phenylchloronitrobenzamides (PCNBs), a novel class of compounds active against the species of trypanosomes that cause Human African Trypanosomiasis (HAT). Herein, we explored the potential to adjust the reactivity of the electrophilic chloronitrobenzamide core. These studies identified compound 7d that potently inhibited the growth of trypanosomes (EC50=120nM for Trypanosoma b. brucei, 18nM for Trypanosoma b. rhodesiense, and 38nM for Trypanosoma b. gambiense) without significant cytotoxicity against mammalian cell lines (EC50>25µM for HepG2, HEK293, Raji, and BJ cell lines) and also had good stability in microsomal models (t1/2>4h in both human and mouse). Overall these properties indicate the compound 7d and its analogs are worth further exploration as potential leads for HAT.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
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Trypanosoma brucei brucei
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Benzamidas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article