Reactivity and Selectivity of dinuclear imine-copper(II) complexes toward melanomas: melanogenesis and structural features influence

Resumen

The cytotoxicity of dinuclear imine-copper(II) complexes, and its analogous mononuclear complexes (see examples at Figure 1), toward different melanoma cells, particularly human SKMEL-05 and SKMEL-147, was investigated [1]. Complex 2, a tyrosinase mimic [2], showed much higher activity in comparison to its analog complex 1, and its reactivity was verified to be remarkably activated by UVB-light, while the mononuclear compound showed a small or negligible effect. Further, a significant dependence on the melanin content in the tumor cells, both from intrinsic pigmentation or stimulated by irradiation, was observed in the case of complex 2 [3]. Similar tests with keratinocytes and melanocytes indicated a much lower sensitivity to both copper(II) complexes, even after exposition to UV light. The process also involves generation of reactive oxygen species (ROS), as verified by EPR spectroscopy, and by using fluorescence indicators. Cytotoxicity is mediated by reactive oxygen species but depends also on melanogenesis, and on interaction with melanin. However, in complexes where the magnetic interaction between the copper centers are not efficient (as in complex 4 at Figure1), the increase in reactivity or sensibility to melanin was not verified.

The results indicated that different mechanisms of action are envolved, depending on the nuclearity and structural features of these complexes. Therefore, dinuclear copper complexes could constitute a potential therapeutic approach against melanoma cancer, devising alternative targets and diversified mechanisms.
Acknowledgements: FAPESP- CEPID Redoxoma, CNPq, CAPES
References
1) Nunes, C.J. et al., Chem.-Biol. Interact. 311 (2019) 108789.