Copper conjugates of nimesulide Schiff bases targeting VEGF, COX and Bcl-2 in pancreatic cancer cells.

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.

• Authors: Vinita Ambike, Shreelekha Adsule, Fakhara Ahmed, Zhiwei Wang, Zahra Afrasiabi, Ekkehard Sinn, Fazlul Sarkar, Subhash Padhye
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 101 Issue 10 Pg. 1517-24 (Oct 2007) ISSN: 0162-0134 [Print] United States
• PMID: 17689613 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Schiff Bases
• Sulfonamides
• Vascular Endothelial Growth Factor A
• Copper
• Cyclooxygenase 2
• nimesulide

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Copper (chemistry)
• Cyclooxygenase 2 (chemistry)
• Electron Spin Resonance Spectroscopy
• Humans
• Models, Molecular
• Proto-Oncogene Proteins c-bcl-2 (chemistry)
• Schiff Bases
• Spectrophotometry, Infrared
• Sulfonamides (chemistry)
• Vascular Endothelial Growth Factor A (chemistry)