Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives.
The reaction of [Cu(dien)NO(3)]NO(3) 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)NO(3))]NO(3); (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)NO(3))](NO(3)) 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)NO(3))](NO(3)), 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.
Bolos
C A
CA
Laboratory of General and Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54006, Greece. bolos@chem.auth.gr
Papazisis
K T
KT
Kortsaris
A H
AH
Voyatzi
S
S
Zambouli
D
D
Kyriakidis
D A
DA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003300:Copper / Q000737:chemistry* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011073:Polyamines / Q000737:chemistry; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D007093:Imidazoles; D008024:Ligands; D009942:Organometallic Compounds; D011073:Polyamines; D013844:Thiazoles; C005391:diethylenetriamine; D003300:Copper