Copper conjugates of nimesulide Schiff bases targeting VEGF, COX and Bcl-2 in pancreatic cancer cells.
J Inorg Biochem
; 101(10): 1517-24, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17689613
ABSTRACT
Copper conjugates of Schiff base derivatives of nimesulide (1), a well-known cyclooxygenase-2 (COX-2) inhibitor, were synthesized, structurally characterized and evaluated for their COX selectivity indices and cytotoxicities on pancreatic tumor, BxPC-3 (COX-2 positive) and MiaPaCa (COX-2 negative) cell lines. Copper conjugates exhibit distorted square planar geometries as revealed by the single crystal X-ray structure determination of Cu(L1)(2) and show significant growth inhibition in both cell lines (IC50 values 3-26 microM for COX-2 positive and 5-9 microM for COX-2 negative cell line) than the parent nimesulide (35 microM for COX-2 positive and >100 microM for COX-2 negative cell line). The mechanistic pathway for the biological activity involves inhibition of vascular endothelial growth factor (VEGF) and COX inhibition, as well as down regulation of antiapoptotic Bcl-2 and Bcl-(XL) proteins.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bases de Schiff
/
Sulfonamidas
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Cobre
/
Fator A de Crescimento do Endotélio Vascular
/
Ciclo-Oxigenase 2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Inorg Biochem
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Índia