title: Acridine conjugates of 3-clip-phen: influence of the linker on the synthesis and the DNA cleavage activity of their copper complexes.
abstract: To increase the DNA cleavage activity and the cell delivery of the bis(phenanthroline) DNA cleaver "3-Clip-Phen", conjugates between 3-Clip-Phen and the intercalators acridine and 6-chloro-2-methoxyacridine, through amino acid linkers of various length, were prepared. After complexation with CuCl(2), the ability of these conjugates to cleave phiX 174 DNA in the presence of a reductant and air was compared. The results indicated that (i) the coupling of 3-Clip-Phen to an acridine derivative increased the DNA cleavage efficiency of the copper complexes, (ii) the acridine derivatives were more active than 6-chloro-2-methoxyacridine derivatives, (iii) the linker length influenced cleavage efficiency, the highest DNA cleavage activity being obtained for an aminocaproic spacer.
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Boldron
authors.forename: Steven A
authors.initials: SA
authors.lastname: Ross
authors.forename: Marguerite
authors.initials: M
authors.lastname: Pitié
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D000166:Acridines / Q000737:chemistry*; D001435:Bacteriophages / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D006868:Hydrolysis / Q000187:drug effects; D007364:Intercalating Agents / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; C115240:Clip-phen; D003432:Cross-Linking Reagents; D007364:Intercalating Agents; D010618:Phenanthrolines; D003300:Copper