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

Mark O'Connor; Andrew Kellett; Malachy McCann; Georgina Rosair; Mary McNamara; Orla Howe; Bernadette S. Creaven; Siobhán McClean; Agnieszka Foltyn-Arfa Kia; Denis O'Shea; Michael Devereux

doi:10.1021/jm201041d

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

Mark O'Connor
, Andrew Kellett
, Malachy McCann
, Georgina Rosair
, Mary McNamara
, Orla Howe
, Bernadette S. Creaven
, Siobhán McClean
, Agnieszka Foltyn-Arfa Kia
, Denis O'Shea
, Michael Devereux

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1957-1968
Number of pages	12
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	5
DOIs	https://doi.org/10.1021/jm201041d
Publication status	Published - 8 Mar 2012

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O'Connor, M., Kellett, A., McCann, M., Rosair, G., McNamara, M., Howe, O., Creaven, B. S., McClean, S., Foltyn-Arfa Kia, A., O'Shea, D., & Devereux, M. (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. Journal of Medicinal Chemistry, 55(5), 1957-1968. https://doi.org/10.1021/jm201041d

O'Connor, Mark ; Kellett, Andrew ; McCann, Malachy et al. / 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. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 5. pp. 1957-1968.

@article{349e7394a52142e8b442fb1bc352c1ed,

title = "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",

abstract = "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.",

author = "Mark O'Connor and Andrew Kellett and Malachy McCann and Georgina Rosair and Mary McNamara and Orla Howe and Creaven, \{Bernadette S.\} and Siobh{\'a}n McClean and \{Foltyn-Arfa Kia\}, Agnieszka and Denis O'Shea and Michael Devereux",

year = "2012",

month = mar,

day = "8",

doi = "10.1021/jm201041d",

language = "English",

volume = "55",

pages = "1957--1968",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "5",

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O'Connor, M, Kellett, A, McCann, M, Rosair, G, McNamara, M , Howe, O , Creaven, BS, McClean, S, Foltyn-Arfa Kia, A, O'Shea, D & Devereux, M 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', Journal of Medicinal Chemistry, vol. 55, no. 5, pp. 1957-1968. https://doi.org/10.1021/jm201041d

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. / O'Connor, Mark; Kellett, Andrew; McCann, Malachy et al.
In: Journal of Medicinal Chemistry, Vol. 55, No. 5, 08.03.2012, p. 1957-1968.

Research output: Contribution to journal › Article › peer-review

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 -

O'Connor M, Kellett A, McCann M, Rosair G, McNamara M , Howe O et al. 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. Journal of Medicinal Chemistry. 2012 Mar 8;55(5):1957-1968. doi: 10.1021/jm201041d