title: Synthesis, characterization and potent DNA-cleaving activity of copper(II)-complexed berberine carboxylate.
abstract: 9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO(3))(2)·3H(2)O, and established as [Cu(CBB)(2)](NO(3))(2)·2H(2)O by means of (1)H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species. Kinetic assay afforded the maximal first-order rate constant k(max) of 2.41 h(-1) and Michaelis constant K(M) of 2.64 mM, respectively, representing ca. 10(8)-fold acceleration in the cleavage. This catalytic efficacy is attributed to the Cu(II)-assisted formation of dimeric species, in which the two berberine subunits cooperatively bind to DNA, whereas the carboxylate-coordinated Cu(II) moiety functions as the cleavage-active center.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Wei-Er
authors.initials: WE
authors.lastname: Lin
authors.forename: Ming-Zhen
authors.initials: MZ
authors.lastname: Chen
authors.forename: Chun-Qiong
authors.initials: CQ
authors.lastname: Zhou
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D007700:Kinetics
chemical_list: D002264:Carboxylic Acids; D056831:Coordination Complexes; D001599:Berberine; C115958:berberrubine; D003300:Copper; D004247:DNA