Copper(II) complexes of salicylic acid combining superoxide dismutase mimetic properties with DNA binding and cleaving capabilities exhibit low toxicity and display promising chemotherapeutic potential with fast acting in-vitro cytotoxicity against cisplatin sensitive and resistant cancer cell lines

O'Connor M., Kellett A., McCann M., Rosair G., McNamara M., Howe O., Creaven B., McClean S., Foltyn-Arfa Kia A., O'Shea D., Devereux M. 

Journal of Medicinal Chemistry55 (5), 1957-1968, 2012.

Abstract: The complexes [Cu(salH)2(H2O)] (1), [Cu(dipsH)2(H2O)] (2), {Cu(3-MeOsal)(H2O)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)]·H2O (7), and [Cu(3-MeOsal)(phen)]·H2O (8) (salH(2) = salicylic acid; dipsH2 = 3,5-diisopropylsalicylic acid; 3-MeOsalH2 = 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.