title: Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes.
abstract: Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] (1) and [Cu(acac)(dppz)Cl] (2) (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) >1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC(50) values of 5.25±0.83 μM (1) and 4.40±0.52 μM (2) in the natural light, and 2.57±0.92 μM (1) and 2.18±0.52 μM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.
authors.affiliation: Department of Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Gong-Jun
authors.initials: GJ
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.forename: Pei-Qi
authors.initials: PQ
authors.lastname: Qiao
authors.forename: Guang-Jun
authors.initials: GJ
authors.lastname: Xu
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Xu
authors.forename: Jin-Lei
authors.initials: JL
authors.lastname: Tian
authors.forename: Wen
authors.initials: W
authors.lastname: Gu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage / Q000187:drug effects* / Q000528:radiation effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003300:Copper; D004247:DNA; C427203:calf thymus DNA