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Mono and dinuclear platinum and palladium complexes containing adamantane–azole ligands: DNA and BSA interaction and cytotoxicity

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Abstract

Synthesis of dinuclear oxadiazole–adamantane platinum(II) and palladium(II) complexes (PtO, PdO) and mononuclear thiazolidine derivative complexes (PtT, PdT) was described. Characterization was performed by elemental analysis, infrared, UV–visible, 1H, 13C, 195Pt NMR spectra, MS spectroscopy and single crystal X-ray diffraction. The cytotoxicity by MTT assay against tumor and normal cell lines with or without extracellular GSH was also investigated. In general, mononuclear complexes containing thiazolidine–adamantane ligands were more cytotoxic than oxadiazole–adamantane derivatives. PtT complex proved to be as active as cisplatin. Dinuclear compounds were considered inactive to cells in evaluated conditions, due to their high stability with ligands in a chelated and bridged way. Results suggest that GSH cannot be considered a target. DNA- and BSA-binding interactions were evaluated using UV–visible and fluorescence spectroscopy, intercalating dyes and molecular docking. Upon coordination to platinum(II), the cytotoxic effect was appreciably improved against tested cell lines, in comparison to free thiazolidine ligand. Comparing thiazolidine derivatives, it is noticeable that the less active compound (PdT) presents stronger interaction with BSA, while PtT has the weaker interaction with BSA and relatively strong binding to isolated DNA, resulting in the most cytotoxic complex. This work shows that the presence of metal is significant but it should be available for interaction. The high lability of palladium complex made this stay retainable in BSA and two metal atoms do not increase activity if it is not able to do any interaction.

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Acknowledgements

The authors gratefully acknowledge FAPEMIG and CNPq for fellowships. M. T. Quezado thanks Laboratório Institucional de Pesquisa, Centro de Laboratórios Multiusuários, Laboratório Multiusuário de Proteômica (LIPq/CELAM, LMProt) da Universidade Federal de Minas Gerais. B. A. Iglesias thanks CNPq 409150/2018-5 and 304711/2018-7. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES/PROEX)—Finance Code 001.

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Authors and Affiliations

  1. Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Ana Luiza de Andrade Querino, Jessika Thayanne da Silva, Josiane Teixeira Silva, Gustavo Miguel Alvarenga, Renata Diniz & Heveline Silva

  2. Laboratório de Bioinorgânica e Materiais Porfirínicos, Department of Chemistry, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Carolina Hahn da Silveira & Bernardo Almeida Iglesias

  3. Department of Biochemistry and Imunology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Mariana Torquato Quezado de Magalhães

  4. Instituto SENAI de Inovação em Química Verde, Rua Morais e Silva, 53, Maracanã, Rio de Janeiro, RJ, 20271-030, Brazil

    Otávio Augusto Chaves

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  1. Ana Luiza de Andrade Querino
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de Andrade Querino, A.L., da Silva, J.T., Silva, J.T. et al. Mono and dinuclear platinum and palladium complexes containing adamantane–azole ligands: DNA and BSA interaction and cytotoxicity. J Biol Inorg Chem 24, 1087–1103 (2019). https://doi.org/10.1007/s00775-019-01719-5

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