Design, synthesis and evaluation of phthalazinone thiohydantoin-based derivative as potent PARP-1 inhibitors.
Bioorg Chem
; 91: 103181, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31404795
ABSTRACT
Two new series of compounds were designed and synthesized as potent PARP-1 inhibitors. These compounds were evaluated for PARP-1 enzyme and cellular inhibitory activities. All efforts lead to the identification of 9k (named as LG-12) with efficient potency both for PARP-1 and BRCA1 deficient MDA-MB-436 cells. Additionally, the novel PARP-1 inhibitor LG-12 is an efficient chemosensitizer, which could potentiate the anti-cancer effect of TMZ. Our data presented herein provide a comprehensive preclinical in vitro evaluation of the potential therapeutic efficacy and potency of chemotherapeutic agent-PARP-1 inhibitor combinations for LG-12. The combined results indicated that LG-12 could be a promising candidate for further study.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ftalazinas
/
Tioidantoínas
/
Neoplasias da Mama
/
Desenho de Fármacos
/
Inibidores de Poli(ADP-Ribose) Polimerases
/
Poli(ADP-Ribose) Polimerase-1
/
Imidazóis
Tipo de estudo:
Evaluation_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China