title: Synthesis, DNA-cleaving activities and cytotoxicities of C₂-symmetrical dipyrrole-polyamide dimer-based Cu(II) complexes: a comparative study.
abstract: Two C₂-symmetrical dipyrrole-polyamide dimers 2 and 3 that were tethered with triethylenetetramine and spermine, respectively, and their corresponding Cu(II) complexes 2@Cu(2+) and 3@Cu(2+), were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicated that both Cu(II) complexes exhibited potent DNA-cleaving activities under physiological conditions, most probably via an oxidative mechanism. Kinetic assay indicate that 2@Cu(2+) and 3@Cu(2+) exhibited comparable catalytic efficiency with the Cu(II) complex of their 2,2'-(ethane-1,2-diylbis(oxy))diethanamine-tethered analog 1. The finding that compounds 2 and 3 showed higher Cu(II) ion-complexing abilities than compound 1, suggests that strong metal complexation does not necessarily lead to an enhancement in the catalytic efficiency of a DNA-cleaving agent. In addition, three Cu(II) complexes displayed moderate inhibitory activities toward three tumor cell lines.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Chun-Qiong
authors.initials: CQ
authors.lastname: Zhou
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Yang
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects*; D019281:Dimerization; D006801:Humans; D009757:Nylons / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009757:Nylons; D009942:Organometallic Compounds; D011758:Pyrroles; D003300:Copper; D004247:DNA
keywords: Cu(II) complex; Cytotoxicity; DNA cleavage; Dipyrrole-polyamide; Polyamine