title: Preparation and pharmacochemical evaluation of mixed ligand copper(II) complexes with triethanolamine and thiophenyl-2 saturated carboxylic acids.
abstract: The dinuclear complex [Cu(2)(L(1))(2)(H(2)tea)(2)] (1) as well as the linear trinuclear complexes [Cu(3)(L(1))(4)(H(2)tea)(2)] (2), [Cu(3)(L(2))(4)(H(2)tea)(2)] (3) and [Cu(3)(L(1))(2)(H(2)tea)(2)(NO(3))(2)] (4) where L(1) = 2-thiophene carboxylato, L(2) = 2-thiophene acetato and H(2)tea = the single deprotonated form of triethanolamine have been prepared and pharmacochemically studied. The crystal structure of 1 is also reported. In vitro antioxidant activity of free ligands and their respective copper complexes includes: a) interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical, b) the ΗΟ˙ mediated oxidation of DMSO, c) scavenging of superoxide anion radicals, d) inhibition of lipid peroxidation and e) soybean lipoxygenase inhibition. The results indicate selectivity of the complexes to different free radicals as a consequence of their physichochemical features. The majority of the complexes 1, 2, 3, 4 effectively inhibit lipid peroxidation. The trinuclear complex 3 is by far the most active with IC(50)=10 μM, within the set, followed by complexes 1 and 2. The complexes were evaluated for their efficacy as anticancer agents against different cancer and normal human cell lines. Results showed that, these compounds mediate a moderate cytotoxic response to normal and cancer cell lines tested and induce cell cycle arrest in G2/M phase of the cell cycle. Flow cytometric analysis suggested that the tested compounds can induce apoptosis.
authors.affiliation: Department of General and Inorganic Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Z
authors.initials: Z
authors.lastname: Boulsourani
authors.forename: G D
authors.initials: GD
authors.lastname: Geromichalos
authors.forename: K
authors.initials: K
authors.lastname: Repana
authors.forename: E
authors.initials: E
authors.lastname: Yiannaki
authors.forename: V
authors.initials: V
authors.lastname: Psycharis
authors.forename: C P
authors.initials: CP
authors.lastname: Raptopoulou
authors.forename: D
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.forename: E
authors.initials: E
authors.lastname: Pontiki
authors.forename: C
authors.initials: C
authors.lastname: Dendrinou-Samara
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry*; D005434:Flow Cytometry; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D016195:G2 Phase; D006801:Humans; D008024:Ligands; D015227:Lipid Peroxidation; D010851:Picrates / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D002264:Carboxylic Acids; D056831:Coordination Complexes; D004983:Ethanolamines; D005609:Free Radicals; D008024:Ligands; D010851:Picrates; D013481:Superoxides; D003300:Copper; C009546:triethanolamine; C004931:1,1-diphenyl-2-picrylhydrazyl; D004121:Dimethyl Sulfoxide