Copper Conjugates of Nimesulide Schiff Bases Targeting VEGF, COX and Bcl-2 in Pancreatic Cancer Cells
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 μM for COX-2 positive and 5-9 μM for COX-2 negative cell line) than the parent nimesulide (35 μM for COX-2 positive and >100 μM 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. © 2007 Elsevier Inc. All rights reserved.
V. Ambike et al., "Copper Conjugates of Nimesulide Schiff Bases Targeting VEGF, COX and Bcl-2 in Pancreatic Cancer Cells," Journal of Inorganic Biochemistry, Elsevier, Jan 2007.
The definitive version is available at http://dx.doi.org/10.1016/j.jinorgbio.2007.06.028
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© 2007 Elsevier, All rights reserved.