Antitumor agents. 284. New desmosdumotin B analogues with bicyclic B-ring as cytotoxic and antitubulin agents.
J Med Chem
; 54(5): 1244-55, 2011 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-21284385
ABSTRACT
We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI(50) values of 0.8-2.1 µM. In contrast, 1 analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) overexpressing multidrug resistant cell line. We have now prepared and evaluated 1 analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI(50) values of 0.06-0.16 µM, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC(50) value of 2.0 µM and colchicine binding by 78% as well as cellular microtubule polymerization and spindle formation.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
Cromonas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos