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

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• 作者：Vinita Ambike ; Shreelekha Adsule ; Fakhara Ahmed ; Zhiwei Wang ; Zahra Afrasiabi ; Ekkehard Sinn ; Fazlul Sarkar ; Subhash Padhye
• 关键词：Nimesulide ; Cyclooxygenase ; BxPC-3 ; MiaPaCa-2 ; Copper complexes
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：101
• 期：10
• 页码：1517-1524
• 全文大小：487 K

文摘

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.