Antiproliferative activity and QSAR study of copper(II) mixed chelate [Cu(N–N)(acetylacetonato)]NO₃ and [Cu(N–N)(glycinato)]NO₃ complexes, (Casiopeínas^&#x

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• 作者：Marí ; a Elena Bravo-Gó ; mez ; Juan Carlos Garcí ; a-Ramos ; Isabel Gracia-Mora ; Lena Ruiz-Azuara
• 关键词：Mixed chelate complexes ; Copper(II) ; Casiopeí ; nas ; Anticancer agents ; QSAR
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：103
• 期：2
• 页码：299-309
• 全文大小：473 K

文摘

Mixed chelate copper(II) complexes patented and mark title registered as Casiopeínas^® are antineoplastic agents with general formulas [Cu(N–N)(α-l-amino acidato)]NO₃ and [Cu(N–N)(O–O)]NO₃, 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)]NO₃ and [Cu(N–N)(gly)]NO₃ 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.