Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands

Ívina P. de Souza; Ariane C.C. de Melo; Bernardo L. Rodrigues; Adailton Bortoluzzi; Simon Poole; Zara Molphy; Vickie McKee; Andrew Kellett; Rodrigo B. Fazzi; Ana M. da Costa Ferreira; Elene C. Pereira-Maia

doi:10.1016/j.jinorgbio.2023.112121

Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands

Ívina P. de Souza, Ariane C.C. de Melo, Bernardo L. Rodrigues, Adailton Bortoluzzi, Simon Poole, Zara Molphy, Vickie McKee, Andrew Kellett, Rodrigo B. Fazzi, Ana M. da Costa Ferreira, Elene C. Pereira-Maia^*

^*Kontaktforfatter

Institut for Fysik, Kemi og Farmaci

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Five ternary copper(II) complexes, [Cu₂(phen)₂(L1)(ClO₄)₂] (1), [Cu₂(phen)₂(L1)(DMSO)₂](PF6)₂ (2), [Cu₂(bpy)₂(L1)(ClO₄)₂(H₂O)₂] (3), [Cu₂(dmp)₂(L1)(ClO₄)₂(H₂O)₂] (4), and [Cu(phen)(L2)]₂(ClO₄)₂ (5), in which phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H₂L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4–5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC₅₀ values of 1.13, 10.60, 0.078, and 1.84 μmol L⁻¹, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.

Originalsprog	Engelsk
Artikelnummer	112121
Tidsskrift	Journal of Inorganic Biochemistry
Vol/bind	241
ISSN	0162-0134
DOI	https://doi.org/10.1016/j.jinorgbio.2023.112121
Status	Udgivet - apr. 2023

Bibliografisk note

Funding Information:
We acknowledge CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) , Grant No. 437298/2018 3 , FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais, Brazil) , Grant No. APQ 01668 18 , the INCT Catálise (Instituto Nacional de Ciência e Tecnologia de Catálise em Sistemas Moleculares e Nanoestruturados), FINEP, and CAPES for financial support and fellowships. We are also grateful for funding from the Carlsberg Foundation grant CF15-0675 for the X-ray diffractometer and to the University of Southern Denmark/Danish Council for Independent Research|Natural Sciences (grant 4181-00329 ) for a visiting professorship (to VMcK). RBF and AMDCF are thankful to São Paulo State Research Foundation (FAPESP, Redoxoma Project, grant 2013/07937-8 ) for EPR equipment maintenance. AK acknowledges funding from Science Foundation Ireland awards 15/CDA/3648 and 12/RC/2275_P2 , the Irish Research Council awards GOIPG/2020/472 and IRCLA/2022/3815 , and the Novo Nordisk Foundation award NNF19OC0056845 .

Publisher Copyright:
© 2023 Elsevier Inc.

Dokumenter og links

10.1016/j.jinorgbio.2023.112121

Citationsformater

de Souza, Í. P., de Melo, A. C. C., Rodrigues, B. L., Bortoluzzi, A., Poole, S., Molphy, Z., McKee, V., Kellett, A., Fazzi, R. B., da Costa Ferreira, A. M., & Pereira-Maia, E. C. (2023). Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands. Journal of Inorganic Biochemistry, 241, Artikel 112121. https://doi.org/10.1016/j.jinorgbio.2023.112121

@article{0dd450478b274c209cd2e085a4c1a7ae,

title = "Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands",

abstract = "Five ternary copper(II) complexes, [Cu2(phen)2(L1)(ClO4)2] (1), [Cu2(phen)2(L1)(DMSO)2](PF6)2 (2), [Cu2(bpy)2(L1)(ClO4)2(H2O)2] (3), [Cu2(dmp)2(L1)(ClO4)2(H2O)2] (4), and [Cu(phen)(L2)]2(ClO4)2 (5), in which phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H2L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4–5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC50 values of 1.13, 10.60, 0.078, and 1.84 μmol L−1, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.",

keywords = "Anthraquinone, Copper complexes, Cytotoxicity, DNA, N'N-heterocyclic ligands, Topoisomerase",

author = "{de Souza}, {{\'I}vina P.} and {de Melo}, {Ariane C.C.} and Rodrigues, {Bernardo L.} and Adailton Bortoluzzi and Simon Poole and Zara Molphy and Vickie McKee and Andrew Kellett and Fazzi, {Rodrigo B.} and {da Costa Ferreira}, {Ana M.} and Pereira-Maia, {Elene C.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = apr,

doi = "10.1016/j.jinorgbio.2023.112121",

language = "English",

volume = "241",

journal = "Journal of Inorganic Biochemistry",

issn = "0162-0134",

publisher = "Elsevier",

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TY - JOUR

T1 - Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands

AU - de Souza, Ívina P.

AU - de Melo, Ariane C.C.

AU - Rodrigues, Bernardo L.

AU - Bortoluzzi, Adailton

AU - Poole, Simon

AU - Molphy, Zara

AU - McKee, Vickie

AU - Kellett, Andrew

AU - Fazzi, Rodrigo B.

AU - da Costa Ferreira, Ana M.

AU - Pereira-Maia, Elene C.

PY - 2023/4

Y1 - 2023/4

N2 - Five ternary copper(II) complexes, [Cu2(phen)2(L1)(ClO4)2] (1), [Cu2(phen)2(L1)(DMSO)2](PF6)2 (2), [Cu2(bpy)2(L1)(ClO4)2(H2O)2] (3), [Cu2(dmp)2(L1)(ClO4)2(H2O)2] (4), and [Cu(phen)(L2)]2(ClO4)2 (5), in which phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H2L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4–5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC50 values of 1.13, 10.60, 0.078, and 1.84 μmol L−1, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.

AB - Five ternary copper(II) complexes, [Cu2(phen)2(L1)(ClO4)2] (1), [Cu2(phen)2(L1)(DMSO)2](PF6)2 (2), [Cu2(bpy)2(L1)(ClO4)2(H2O)2] (3), [Cu2(dmp)2(L1)(ClO4)2(H2O)2] (4), and [Cu(phen)(L2)]2(ClO4)2 (5), in which phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine, dmp = 2,9-dimethyl-1,10-phenanthroline, H2L1 = 1,4-dihydroxyanthracene-9,10-dione and HL2 = 1-hydroxyanthracene-9,10-dione, DMSO = dimethylsulfoxide, were synthesized and fully characterized. Complex 2 was obtained through the substitution of perchlorate for DMSO. When two hydroxyquinone groups are present, L1 makes a bridge between two Cu(II) ions, which also bind two nitrogens of the respective diimine ligand. The compounds bind to calf thymus DNA and oxidatively cleave pUC19 DNA according to the following order of activity 1 > 4–5 > 3. Furthermore, complexes 1, 3, 4 and 5 inhibit topoisomerase-I activity and the growth of myelogenous leukemia cells with the IC50 values of 1.13, 10.60, 0.078, and 1.84 μmol L−1, respectively. Complexes 1 and 4 are the most active in cancer cells and in DNA cleavage.

KW - Anthraquinone

KW - Copper complexes

KW - Cytotoxicity

KW - DNA

KW - N'N-heterocyclic ligands

KW - Topoisomerase

U2 - 10.1016/j.jinorgbio.2023.112121

DO - 10.1016/j.jinorgbio.2023.112121

M3 - Journal article

C2 - 36696836

AN - SCOPUS:85146561837

SN - 0162-0134

VL - 241

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

M1 - 112121

ER -

Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands

Abstract

Bibliografisk note

Dokumenter og links

Fingeraftryk

Citationsformater