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

Citation data:

Journal of inorganic biochemistry, ISSN: 0162-0134, Vol: 101, Issue: 10, Page: 1517-24

Publication Year:
2007
Usage 44
Abstract Views 44
Captures 27
Readers 24
Exports-Saves 3
Citations 37
Citation Indexes 37
Repository URL:
http://scholarsmine.mst.edu/chem_facwork/625
PMID:
17689613
DOI:
10.1016/j.jinorgbio.2007.06.028
Author(s):
Ambike, Vinita; Adsule, Shreelekha; Ahmed, Fakhara; Wang, Zhiwei; Afrasiabi, Zahra; Sinn, Ekkehard; Sarkar, Fazlul; Padhye, Subhash
Publisher(s):
Elsevier BV; Elsevier
Tags:
Biochemistry, Genetics and Molecular Biology; Chemistry; copper complex; cyclooxygenase 2 inhibitor; nimesulide; prostaglandin synthase; protein bcl 2; protein bcl xl; Schiff base; vasculotropin; article; controlled study; drug cytotoxicity; drug structure; drug synthesis; enzyme inhibition; human; human cell; pancreas cancer; structure analysis; X ray crystallography; Animals; Cell Line; Tumor; Cell Proliferation; Copper; Cyclooxygenase 2; Electron Spin Resonance Spectroscopy; Humans; Models; Molecular; Proto-Oncogene Proteins c-bcl-2; Schiff Bases; Spectrophotometry; Infrared; Sulfonamides; Vascular Endothelial Growth Factor A; BxPC-3; Copper complexes; Cyclooxygenase; MiaPaCa-2; Nimesulide; copper complex; cyclooxygenase 2 inhibitor; nimesulide; prostaglandin synthase; protein bcl 2; protein bcl xl; Schiff base; vasculotropin; article; controlled study; drug cytotoxicity; drug structure; drug synthesis; enzyme inhibition; human; human cell; pancreas cancer; structure analysis; X ray crystallography; Animals; Cell Line, Tumor; Cell Proliferation; Copper; Cyclooxygenase 2; Electron Spin Resonance Spectroscopy; Humans; Models, Molecular; Proto-Oncogene Proteins c-bcl-2; Schiff Bases; Spectrophotometry, Infrared; Sulfonamides; Vascular Endothelial Growth Factor A; BxPC-3; Copper complexes; Cyclooxygenase; MiaPaCa-2; Nimesulide
article description
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.