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A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging

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Abstract

A novel fluorescent ligand (H2LCl⋅1.5CH3OH, 1) was synthesized and metal complexes of 1 with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)2Cl2 (2), Fe(HL)2Cl3⋅3H2O (3), Ni(L)(HL)Cl⋅8H2O (4), Cu(HL)Cl2⋅4H2O (5), Zn(H2L)Cl3 (6), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of 4 nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex 5 exhibited excellent activity against both cancer cells with low IC50 value 22.18 ± 0.35 μg/mL (35.66 ± 0.56 μM) for SW-872 and 79.41 ± 3.54 μg/mL (127.6 ± 5.69 μM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G1 and S phases for complex 5 against MCF-7 and SW-872 cancer cells, while complex 6 could arrest the MCF-7 and SW-872 cells in G2 and G1 phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.

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Acknowledgements

We thank the University of Tabriz-Iran and Iran National Science Foundation (INSF) for funding aspect of this present research. Also, we would like to thank Ardabil University of Medical Sciences and Immunology Research Center of Tabriz University of Medical Sciences. The authors kindly thank the project SOLID21 CZ.02.1.01/0.0/0.0/16_019/0000760 from Operational Programme Research, Development and Education financed by European Structural and Investment Funds and the Czech Ministry of Education, Youth and Sports for supporting the crystallographic part of this work.

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Authors and Affiliations

  1. Department of Inorganic Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, 51666-14766, Iran

    Sima Feizpour & Seyed Abolfazl Hosseini-Yazdi

  2. Department of Microbiology and Immunology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

    Elham Safarzadeh

  3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, 5166614731, Iran

    Behzad Baradaran

  4. Institute of Physics of the Czech Academy of Sciences, Na Slovance 2, 182 21, Prague 8, Czech Republic

    Michal Dusek & Morgane Poupon

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  1. Sima Feizpour
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Correspondence to Seyed Abolfazl Hosseini-Yazdi.

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775_2023_2001_MOESM1_ESM.pdf

Supplementary file1Supplementary data associated 1H, 13C NMR of 1 and 6 and TGA-DTA diagrams for 2–5. Also, X-ray crystallography section was included. (PDF 4518 KB)

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Feizpour, S., Hosseini-Yazdi, S.A., Safarzadeh, E. et al. A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging. J Biol Inorg Chem 28, 457–472 (2023). https://doi.org/10.1007/s00775-023-02001-5

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