Structural Rigidification of N-Aryl-pyrroles into Indoles Active against Intracellular and Drug-Resistant Mycobacteria.
ACS Med Chem Lett
; 13(1): 63-69, 2022 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-35059125
ABSTRACT
A series of indolyl-3-methyleneamines incorporating lipophilic side chains were designed through a structural rigidification approach and synthesized for investigation as new chemical entities against Mycobacterium tuberculosis (Mtb). The screening led to the identification of a 6-chloroindole analogue 7j bearing an N-octyl chain and a cycloheptyl moiety, which displayed potent in vitro activity against laboratory and clinical Mtb strains, including a pre-extensively drug-resistant (pre-XDR) isolate. 7j also demonstrated a marked ability to restrict the intracellular growth of Mtb in murine macrophages. Further assays geared toward mechanism of action elucidation have thus far ruled out the involvement of various known promiscuous targets, thereby suggesting that the new indole 7j may inhibit Mtb via a unique mechanism.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido