Journal of medicinal chemistry · 2012
Copper(II) complexes of salicylic acid combining superoxide dismutase mimetic properties with DNA binding and cleaving capabilities display promising chemotherapeutic potential with fast acting in vitro cytotoxicity against cisplatin sensitive and resistant cancer cell lines.
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O'Connor Mark, Kellett Andrew, McCann Malachy, Rosair Georgina, McNamara Mary, Howe Orla, Creaven Bernadette S, McClean Siobhán, Kia Agnieszka Foltyn-Arfa, O'Shea Denis, Devereux Michael
Аннотация
The complexes [Cu(salH)(2)(H(2)O)] (1), [Cu(dipsH)(2)(H(2)O)] (2), {Cu(3-MeOsal)(H(2)O)(0.75)}(n) (3), [Cu(dipsH)(2)(BZDH)(2)] (4), [Cu(dipsH)(2)(2-MeOHBZDH)(2)]·EtOH (5), [Cu(sal)(phen)] (6), [Cu(dips)(phen)]·H(2)O (7), and [Cu(3-MeOsal)(phen)]·H(2)O (8) (salH(2) = salicylic acid; dipsH(2) = 3,5-diisopropylsalicylic acid; 3-MeOsalH(2) = 3-methoxysalicylic acid; BZDH = benzimidazole; 2-MeOHBZDH = 2 methanolbenzimidazole and phen =1,10-phenanthroline) were prepared and characterized. Structures of 4, 5, and 8 were determined by X-ray crystallography. Compounds 1-8 are potent superoxide dismutase mimetics, and they are inactive as inhibitors of COX-2 activity. Compounds 1, 4, and 5 exhibit moderate inhibition of COX-1. Complexes 6-8 display rapid micromolar cytotoxicity against cisplatin sensitive (breast (MCF-7), prostate (DU145), and colon (HT29)) and cisplatin resistant (ovarian (SK-OV-3)) cell lines compared to 1-5, and they exhibit potent in vitro DNA binding and cleavage capabilities.
Предметные рубрики MeSH
Antineoplastic AgentsCell Line, TumorCisplatinCoordination ComplexesCopperCrystallography, X-RayCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase InhibitorsDNADNA CleavageDrug Resistance, NeoplasmDrug Screening Assays, AntitumorHumansMolecular MimicryMolecular StructureSalicylatesStructure-Activity RelationshipSuperoxide Dismutase