title: Cytostatic activity of 1,10-phenanthroline derivatives generated by the clip-phen strategy.
abstract: The cytostatic activities of a series of twelve 1,10-phenanthroline (Phen) derivatives and of their copper complexes were studied on L1210 murine leukemia cells. Large increases in the biological activity were observed for compounds of the 3-Clip-Phen series, in which two Phen moieties were bridged at their C3 positions by an alkoxy linker, the 3-pentyl-Clip-Phen derivative showing an IC(50) value of 130 nM while Phen shows an IC(50) value of 2500 nM under the same conditions. IC(50) values seemed to be modulated not only by the position, the nature, and the length of the linker of Clip-Phen but also by hydrophobicity. Since copper complexes of Phen are chemical nucleases and nucleic acids are thus a potential target for these compounds, the corresponding copper complexes were also studied. Copper complexation of the 3-Clip-Phen ligands did not increase their biological activities. Attempts to vectorize 3-Clip-Phen derivatives with a DNA binder such as spermine or with a cell-penetration peptide failed to increase their biological activity relative to the original 3-Clip-Phen series.
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France. pitie@lcc-toulouse.fr
authors.forename: Marguerite
authors.initials: M
authors.lastname: Pitié
authors.forename: Alain
authors.initials: A
authors.lastname: Croisy
authors.forename: Danièle
authors.initials: D
authors.lastname: Carrez
authors.forename: Christophe
authors.initials: C
authors.lastname: Boldron
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C115240:Clip-phen; D010618:Phenanthrolines; D003300:Copper; C028419:cuprous chloride; C025205:1,10-phenanthroline