title: Cu(II)-dipeptide complexes of 2-(4'-thiazolyl)benzimidazole: synthesis, DNA oxidative damage, antioxidant and in vitro antitumor activity.
abstract: Two new Cu(II)-dipeptide complexes of 2-(4'-thiazolyl)benzimidazole, [Cu(Gly-Gly)(TBZ)(Cl)]·4H2O (1) and [Cu(Gly-l-Leu)(TBZ)(Cl)]·H2O (2) (Gly-Gly=glycyl-glycine anion, Gly-l-Leu=glycyl-l-leucine anion and TBZ=2-(4'-thiazolyl)benzimidazole) have been synthesized and characterized by elemental analyses, molar conductance measurements and spectroscopy methods (IR, UV-visible, electrospray ionization mass spectra (ESI-MS) and EPR). The DNA binding and cleavage properties of the complexes monitored by multi-spectroscopic techniques (UV absorption, fluorescence and circular dichroism), viscosity determination and agarose gel electrophoresis indicated that the complexes bound to calf thymus (CT)-DNA via a partial intercalative mode with considerable intrinsic binding constants (Kb=1.64×10(5)M(-1) for 1 and 2.59×10(5)M(-1) for 2), and cleaved pBR322 DNA efficiently in the mediation of ascorbic acid (AA), probably via an oxidative damage mechanism induced by OH. The antioxidant activities of the complexes have been evaluated by means of modified nitroblue tetrazolium (NBT) photoreduction and cellular antioxidant activity (CAA) assays using HepG2 cells as a model, and it was found that IC50 values of 1 and 2 for dismutation of O2(-) were 0.172 and 0.247μM, respectively, and the CAA50 values were 10.57 and 10.74μM. In addition, the complexes were subjected to in vitro cytotoxicity against three human carcinoma cell lines (HeLa, A549 and HepG2), which revealed that the complexes exhibited effective cytotoxicity (IC50 values varying from 33.17 to 100μM) and selective inhibition toward HeLa cell lines. These findings indicate that the complexes have the potential to act as effective metallopeptide chemotherapeutic agents.
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Xia-Bing
authors.initials: XB
authors.lastname: Fu
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gan
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Gao
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou 510642, China; Institute of Biomaterial, South China Agricultural University, Guangzhou 510642, China. Electronic address: lexyfu@163.com.
authors.forename: Xue-Yi
authors.initials: XY
authors.lastname: Le
mesh_terms: D000871:Anthelmintics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D010957:Plasmids / Q000737:chemistry; D013827:Thiabendazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D000970:Antineoplastic Agents; D000975:Antioxidants; D003603:Cytotoxins; D004151:Dipeptides; D003300:Copper; D004247:DNA; D013827:Thiabendazole
keywords: 2-(4′-Thiazolyl)benzimidazole; Antioxidant activity; Cytotoxicity; DNA binding; Metallopeptide complexes; Oxidative damage