Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives

被引:62
作者
Bolos, CA [1 ]
Papazisis, KT
Kortsaris, AH
Voyatzi, S
Zambouli, D
Kyriakidis, DA
机构
[1] Aristotelian Univ Thessaloniki, Dept Chem, Lab Gen & Inorgan Chem, Thessaloniki 54006, Greece
[2] Theagen Canc Hosp, Thessaloniki 54007, Greece
[3] Aristotelian Univ Thessaloniki, Dept Chem, Lab Biochem, Thessaloniki 54006, Greece
关键词
copper complexes; dien; thiazoles; thiazoline; imidazoles; antiproliferative activity; colon cancer;
D O I
10.1016/S0162-0134(01)00344-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The reaction of [Cu(dien)NO3]NO3 with 2-amino-5-methylthiazole (2A5MT), 2-amino-2-thiazoline (2A-2Tzn), imidazole (im), N,N'-thiocarbonyldiimidazole (Tcdim), 2-aminothiazole (2AT) and 2-ethylimidazole (2Etim), gave a new series of mixed-ligand compounds of the general formula [Cu(dien)(B)NO3)]NO3; (dien, diethylenetriamine; B, 2A5MT, 2A-2Tzn, im, Tcdim, 2AT and 2Etim). The complexes have been characterised by elemental analysis, molar conductivity and magnetic measurements, as well as by electronic and IR spectral studies. According to the above measurements the possible structure of the compounds is the square pyramidal in the solid state and the square planar in aqueous solution. We tested all complexes for antiproliferative (cytostatic and cytotoxic) activity against a panel of cell lines (HeLa, L929, HT-29 and T47D). All [(dien)Cu(B)NO3)](NO3) complexes had an activity against colon cancer cells (HT-29), inducing G2/M cell cycle arrest, an effect that for most of the complexes could be attributed to p34cdc2 inhibition by tyrosine-phosphorylation and/or to induction of (cyclin-dependent kinase inhibitor) p21(WAF1). Other cell lines were resistant to the majority of the complexes, except [Cu(dien)(2A5MT)NO3)](NO3). that had showed the highest anti-proliferative activity against HT-29 cells also. The predilection for colon cancer cells and the relatively low toxicity against normal (L929) cells justify further investigation of this group of compounds. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:25 / 36
页数:12
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