Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Cell Line, Tumor
-
Cisplatin / pharmacology*
-
Coordination Complexes / chemical synthesis
-
Coordination Complexes / chemistry
-
Coordination Complexes / pharmacology*
-
Copper*
-
Crystallography, X-Ray
-
Cyclooxygenase 1 / metabolism
-
Cyclooxygenase 2 / metabolism
-
Cyclooxygenase Inhibitors / chemical synthesis
-
Cyclooxygenase Inhibitors / chemistry
-
Cyclooxygenase Inhibitors / pharmacology
-
DNA / metabolism*
-
DNA Cleavage / drug effects
-
Drug Resistance, Neoplasm
-
Drug Screening Assays, Antitumor
-
Humans
-
Molecular Mimicry
-
Molecular Structure
-
Salicylates / chemical synthesis
-
Salicylates / chemistry
-
Salicylates / pharmacology*
-
Structure-Activity Relationship
-
Superoxide Dismutase / metabolism*
Substances
-
Antineoplastic Agents
-
Coordination Complexes
-
Cyclooxygenase Inhibitors
-
Salicylates
-
Copper
-
DNA
-
Cyclooxygenase 1
-
Cyclooxygenase 2
-
Superoxide Dismutase
-
Cisplatin