1.
Bioorg Med Chem
; 11(12): 2617-26, 2003 Jun 12.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12757727
RESUMO
A library of 51 analogues of the naturally occurring protein farnesyltransferase inhibitor pepticinnamin E was investigated biologically. Several compounds with pronounced inhibitory activity were discovered with the lowest IC(50) value reaching 1 microM. The library contains inhibitors which are competitive to either farnesylpyrophosphate or the peptide substrate and a bisubstrate inhibitor. This activity is supported and rationalized by molecular modelling experiments and different binding modes of the inhibitors deduced from them. Several compounds induced apoptosis in a Ras-transformed tumour cell line, and in one case this correlated with farnesyltransferase-inhibiting activity.
Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Cães , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Farnesiltranstransferase , Humanos , Modelos Moleculares , Biblioteca de Peptídeos , Ratos , Relação Estrutura-Atividade , Especificidade por Substrato , Proteínas ras/metabolismo
2.
Angew Chem Int Ed Engl
; 41(19): 3616-20; 3516, 2002 Oct 04.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12370908