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Novel luminescent benzopyranothiophene- and BODIPY-derived aroylhydrazonic ligands and their dicopper(II) complexes: syntheses, antiproliferative activity and cellular uptake studies

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Abstract

Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 1, derived from the BPT-containing ligand H3L1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed. Additionally, the stability of the ligands and complexes was monitored by UV–vis spectroscopy in DMSO and biologically relevant media. All the compounds showed moderate to high cytotoxicity towards the triple negative human breast cancer cell line MDA-MB-231. BPT derivatives were the most cytotoxic, specially H3L1, reaching an IC50 value up to the nanomolar range. Finally, fluorescence microscopy imaging studies employing mitochondria- and nucleus-staining dyes showed that the BODIPY-carrying ligand H3L2 was highly cell permeant and suggested that the compound preferentially accumulates in the mitochondria.

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Acknowledgements

Nicolás A. Rey thanks FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) for the research fellowships awarded. J. P. Rada appreciates the financial support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) through the fellowship PDSE-88881.187965/2018-0 and the scholarship 88887.151652/2017-00, as well as CNPq (GM/GD-140228/2018-7). In addition, Prof. Ricardo Q. Aucélio (Department of Chemistry, PUC-Rio) is gratefully acknowledged for the elemental analyses.

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Authors and Affiliations

  1. LABSO-Bio Laboratory, Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rua Marquês de São Vicente, 225, Rio de Janeiro, 22453-900, Brazil

    Jesica Paola Rada & Nicolás A. Rey

  2. Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, CNRS, 4 place Jussieu, 75005, Paris, France

    Jérémy Forté, Michèle Salmain & Vincent Corcé

  3. Hôpital de la Pitié-Salpêtrière, Inserm U1127, CNRS UMR 7225, Sorbonne Université, 75013, Paris, France

    Geoffrey Gontard & Claude-Marie Bachelet

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  1. Jesica Paola Rada
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Rada, J.P., Forté, J., Gontard, G. et al. Novel luminescent benzopyranothiophene- and BODIPY-derived aroylhydrazonic ligands and their dicopper(II) complexes: syntheses, antiproliferative activity and cellular uptake studies. J Biol Inorg Chem 26, 675–688 (2021). https://doi.org/10.1007/s00775-021-01885-5

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