Reactivity of dinuclear copper(II) complexes towards melanoma cells: Correlation with its stability, tyrosinase mimicking and nuclease activity

Author(s):Show less -

Nunes, Cleia Justin ^[1] ; Borges, Beatriz Essenfelder ^[2] ; Nakao, Lia Sumie ^[2] ; Peyroux, Eugenie ^[3] ; Hardre, Renaud ^[3] ; Faure, Bruno ^[3] ; Reglier, Marius ^[3] ; Giorgi, Michel ^[4] ; Prieto, Marcela Bach ^[5] ; Oliveira, Carla Columbano ^[5] ; Da Costa Ferreira, Ana M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Quim, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Parana, Dept Patol Basica, BR-81531990 Curitiba, Parana - Brazil

^[3] Aix Marseille Univ, Cent Marseille, CNRS, ISM2 UMR 7313, F-13397 Marseille - France

^[4] Aix Marseille Univ, CNRS, Spectropole FR1739, F-13397 Marseille - France

^[5] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 149, p. 49-58, AUG 2015.
• Web of Science Citations: 3

Abstract

In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species was very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Moreover, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/09367-7 - Investigation on the role of metallodrug-carbohydrate interactions in multidrug resistance tumor cells
• Grantee: Ana Maria da Costa Ferreira
• Support type: Research Grants - Visiting Researcher Grant - International