Synthesis and cytotoxic activity of certain trisubstituted azetidin-2-one derivatives as a cis-restricted combretastatin A-4 analogues.
Arch Pharm Res
; 40(1): 13-24, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27747473
ABSTRACT
Novel series of 1,3,4-trisubstituted azetidin-2-one derivatives 8a-p were synthesized and proposed as cytotoxic agents acting via inhibition of tubulin at the colchicine binding site. The design of the target compounds was based upon modification in the structure of the vascular targeting agent combretastatin A-4 (CA-4). The cis double bond linker in CA-4 was replaced with the azetidin-2-one ring aiming to prevent the cis/trans isomerization that suppresses the activity of CA-4, thereby enhancing its antiproliferative activity. All new compounds were investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by four most potent compounds 8g, 8j, 8n and 8o was also evaluated. The synthesis of the final targets was achieved adopting Staudinger reaction. Molecular modeling studies were performed to rationalize the biological results.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Azetidinas
/
Bibenzilas
/
Citotoxinas
Limite:
Humans
Idioma:
En
Revista:
Arch Pharm Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Egito