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Synthesis and biological evaluation of thiosemicarbazone derivatives

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Abstract

In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as a drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 h, and Imatinib was used as the positive control. According to the results of the cytotoxicity assay, it can be said that the five compounds (3b, c, f, g, and m with IC50 = 10.59–9.08 μg/mL; Imatinib IC50 = 11.68 μg/mL) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n, and r with IC50 = 7.02–9.08 μg/mL; Imatinib IC50 = 9.24 μg/mL) had a more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3 m showed the highest antiproliferative effect against C6 and MCF7 cell lines.

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Acknowledgements

This work is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University under the project number SHMYO-013 and Scientific Research Projects Commission of Tokat Gaziosmanpasa University (Project Number: 2019/54).

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Authors and Affiliations

  1. Department of Basic Pharmaceutical Sciences, Cumhuriyet University, Sivas, Turkey

    Murat Doğan

  2. Department of Pharmaceutical Biotechnology, Cumhuriyet University, Sivas, Turkey

    Ümit M. Koçyiğit

  3. Faculty of Science and Arts, Department of Chemistry, Tokat Gaziosmanpaşa University, 60250, Tokat, Turkey

    Meliha Burcu Gürdere, Mustafa Ceylan & Yakup Budak

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  1. Murat Doğan
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  2. Ümit M. Koçyiğit
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  3. Meliha Burcu Gürdere
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  4. Mustafa Ceylan
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  5. Yakup Budak
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Correspondence to Meliha Burcu Gürdere.

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Doğan, M., Koçyiğit, Ü.M., Gürdere, M.B. et al. Synthesis and biological evaluation of thiosemicarbazone derivatives. Med Oncol 39, 157 (2022). https://doi.org/10.1007/s12032-022-01784-y

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