Synthesis and Cytotoxicity Assessment against Human Colorectal Cancer Cell Lines of Quaternary 8-Dichloromethyl Protoberberine Alkaloids.
Chem Biodivers
; 20(6): e202300570, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-37194166
ABSTRACT
Twenty-two quaternary 8-dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol/water partition coefficients by up to values 3-4 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds inâ
vitro. The IC50 values of antiproliferative activity of quaternary 8-dichloromethyl-pseudoberberine 4-chlorobenzenesulfonate and quaternary 8-dichloromethyl-pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31â
µM and 0.41â
µM, respectively, significantly stronger than those of other compounds and positive control 5-fluorouracil. These findings suggest that 8-dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Alcaloides
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Chem Biodivers
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND