Hydropathic analysis and biological evaluation of stilbene derivatives as colchicine site microtubule inhibitors with anti-leukemic activity.
J Enzyme Inhib Med Chem
; 24(6): 1237-44, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19912057
ABSTRACT
The crucial role of the microtubule in cell division has identified tubulin as a target for the development of therapeutics for cancer; in particular, tubulin is a target for antineoplastic agents that act by interfering with the dynamic stability of microtubules. A molecular modeling study was carried out to accurately represent the complex structure and the binding mode of a new class of stilbene-based tubulin inhibitors that bind at the alphabeta-tubulin colchicine site. Computational docking along with HINT (Hydropathic INTeractions) score analysis fitted these inhibitors into the colchicine site and revealed detailed structure-activity information useful for inhibitor design. Quantitative analysis of the results was in good agreement with the in vitro antiproliferative activity of these derivatives (ranging from 3 nM to 100 muM) such that calculated and measured free energies of binding correlate with an r(2) of 0.89 (standard error +/- 0.85 kcal mol(-1)). This correlation suggests that the activity of unknown compounds may be predicted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Leucemia
/
Colchicina
/
Moduladores de Tubulina
/
Microtúbulos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos