Copper conjugates of nimesulide Schiff bases targeting VEGF, COX and Bcl-2 in pancreatic cancer cells |
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Authors: | Ambike Vinita Adsule Shreelekha Ahmed Fakhara Wang Zhiwei Afrasiabi Zahra Sinn Ekkehard Sarkar Fazlul Padhye Subhash |
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Institution: | Department of Chemistry, University of Pune, Pune 411 007, India. |
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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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Keywords: | Nimesulide Cyclooxygenase BxPC-3 MiaPaCa-2 Copper complexes |
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