TY - JOUR
T1 - 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
AU - O'Connor, Mark
AU - Kellett, Andrew
AU - McCann, Malachy
AU - Rosair, Georgina
AU - McNamara, Mary
AU - Howe, Orla
AU - Creaven, Bernadette S.
AU - McClean, Siobhán
AU - Foltyn-Arfa Kia, Agnieszka
AU - O'Shea, Denis
AU - Devereux, Michael
PY - 2012/3/8
Y1 - 2012/3/8
N2 - The complexes [Cu(salH) 2(H 2O)] (1), [Cu(dipsH) 2(H 2O)] (2), {Cu(3-MeOsal)(H 2O) 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 2O (7), and [Cu(3-MeOsal)(phen)] •H 2O (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.
AB - The complexes [Cu(salH) 2(H 2O)] (1), [Cu(dipsH) 2(H 2O)] (2), {Cu(3-MeOsal)(H 2O) 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 2O (7), and [Cu(3-MeOsal)(phen)] •H 2O (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.
UR - https://www.scopus.com/pages/publications/84858034310
U2 - 10.1021/jm201041d
DO - 10.1021/jm201041d
M3 - Article
C2 - 22313179
AN - SCOPUS:84858034310
SN - 0022-2623
VL - 55
SP - 1957
EP - 1968
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 5
ER -
