title: Antiproliferative activity and QSAR study of copper(II) mixed chelate [Cu(N-N)(acetylacetonato)]NO3 and [Cu(N-N)(glycinato)]NO3 complexes, (Casiopeínas).
abstract: Mixed chelate copper(II) complexes patented and mark title registered as Casiopeínas are antineoplastic agents with general formulas [Cu(N-N)(alpha-l-amino acidato)]NO(3) and [Cu(N-N)(O-O)]NO(3), where the N-N donor is an aromatic substituted diimine (1,10-phenanthroline (phen) or 2,2'-bipyridine (bpy)) and the O-O donor is acetylacetonate (acac) or salicylaldehydate (salal). In the present work, the series of complexes [Cu(N-N)(acac)]NO(3) and [Cu(N-N)(gly)]NO(3) with several substituents on the diimine ligand were selected to perform a quantitative structure-activity relationship (QSAR) study. Two main analysis were performed: (1) the study of the influence of the substituents on diimine ligand on physicochemical properties such as half-wave potential (E(1/2)) and their relationship with medial lethal dose (LD50) or medial inhibitory concentration (IC50) on several tumor cell lines and (2) the study of the influence of the secondary ligand when acac is changed for glycinate (gly). Results showed that the presence of the central fused aromatic ring in the phen containing complexes is necessary to preserve the antiproliferative activity. The QSAR equations showed a strong relationship between the IC50 and E(1/2); the most active complexes are the weaker oxidants. The change of secondary ligand from acac to gly has less influence on biological activity than the changes on the diimine ligand.
authors.affiliation: Facultad de Química, Departamento de Química Inorgánica y Nuclear, Universidad Nacional Autónoma de México, Av. Universidad 3000, México, DF 04510, Mexico.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Bravo-Gómez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Ramos
authors.forename: Isabel
authors.initials: I
authors.lastname: Gracia-Mora
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D003300:Copper