Title

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 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.

Department(s)

Chemistry

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2007 Elsevier, All rights reserved.


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