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*


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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.

TidsskriftJournal of Inorganic Biochemistry
StatusUdgivet - 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.


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