Design, synthesis, and biological evaluation of novel chrysin derivatives as poly(ADP-ribose) polymerase 1 (PARP1) inhibitors for the treatment of breast cancer.
Chin J Nat Med
; 22(5): 455-465, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38796218
ABSTRACT
In this study, we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly (ADP-ribose) polymerase 1 (PARP1). Among these derivatives, compound 5d emerged as the most effective chrysin-based inhibitor of PARP1, with an IC50 value of 108 nmol·L-1. This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage. Furthermore, 5d induced apoptosis and caused an extended G1/S-phase in these cell lines. Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1. In vivo, in a xenograft model, 5d effectively reduced tumor growth by downregulating PARP1 expression. Overall, compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Neoplasias da Mama
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Apoptose
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Proliferação de Células
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Inibidores de Poli(ADP-Ribose) Polimerases
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Poli(ADP-Ribose) Polimerase-1
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Chin J Nat Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China