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Dinuclear Copper(I) Complexes Containing Cyclodiphosphazane Derivatives and Pyridyl Ligands: Synthesis, Structural Studies, and Antiproliferative Activity toward Human Cervical and Breast Cancer Cells

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Title Dinuclear Copper(I) Complexes Containing Cyclodiphosphazane Derivatives and Pyridyl Ligands: Synthesis, Structural Studies, and Antiproliferative Activity toward Human Cervical and Breast Cancer Cells
 
Creator BALAKRISHNA, MS
SURESH, D
RAI, A
MAGUE, JT
PANDA, D
 
Subject in-vitro antitumor
metal-complexes
antiinflammatory drugs
coordination chemistry
kinetic stabilization
reversible conversion
microtubule dynamics
molecular-structures
donor ligands
au-i
 
Description Several mixed-ligand copper(I) complexes of cyclodiphosphazanes, [(t)BuNP(NC(4)H(8)X)](2) (1, X = O; 2, X = NMe), were synthesized by reacting the octanuclear copper(I) complexes [Cu(8)(mu(2)-l)(8){[(t)BuNP(NC(4)H(8)X)](2)}(4)] (3, X = O; 4, X = NMe) with various pyridyl ligands. Interaction of the metallomacrocyclic complex 3 or 4 with pyridine, 2,2'-bipyridine, and 1,10-phenanthroline afforded the neutral dinuclear complexes [(C(5)H(5)N)(4)Cu(2)l(2){[(t)BuNP(NC(4)H(8)X)](2)}] (5, X = O; 6, X = NMe), [(2,2'-bpy)2Cu(2)l(2){[(t)BuNP(NC(4)H(8)X)](2)}] (7, X = O; 8, X = NMe), and [(1,10-phen)(2)Cu(2)l(2){[(t)BuNP-(NC(4)H(8)X)](2)}] (9, X =0; 10, X = NMe), respectively, in good yield. The new dinuclear complexes 3, 5, and 7-9 were tested for their cytotoxic propenies against human cervical cancer (HeLa) cells. The results indicated that all of the copper complexes have in vitro antitumor activity either similar to or better than that of cisplatin, a widely used anticancer drug. Among the compounds tested, complex 9 showed the most potent inhibitory activity in HeLa cells. In addition, complex 9 was found to potently inhibit proliferation of human breast cancer cells (MCF-7), highly metastatic breast cancer cells (MDA-MB 231), and nontransformed Chinese hamster ovary (CHO) cells. Complex 9 inhibited proliferation of these cells in culture more potently than cisplatin; for example, complex 9 was found to inhibit proliferation of HeLa and MCF-7 cells 3 and 5 times more efficiently than cisplatin. Complex 9 treatment damaged the DNA integrity, blocked the cells in the G1 phase of the cell cycle, and induced apoptosis via a p53-dependent pathway. The molecular structures of conplexes 9 and 10 were confirmed by single-crystal X-ray diffraction studies.
 
Publisher AMER CHEMICAL SOC
 
Date 2011-07-13T23:18:24Z
2011-12-26T12:47:26Z
2011-12-27T05:54:22Z
2011-07-13T23:18:24Z
2011-12-26T12:47:26Z
2011-12-27T05:54:22Z
2010
 
Type Article
 
Identifier INORGANIC CHEMISTRY, 49(19), 8790-8801
0020-1669
http://dx.doi.org/10.1021/ic100944d
http://dspace.library.iitb.ac.in/xmlui/handle/10054/3799
http://hdl.handle.net/10054/3799
 
Language en