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Synthesis of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-ones, their lipophilicity and anticancer activity in vitro

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Abstract

A new one-step synthesis of novel biologically active 2-substituted 2,4-dihydroxyphenyl-4\(H\)-thieno[3,2-\(d\)][1,3]thiazin-4-ones and 4\(H\)-thieno[2,3-\(d\)][1,3]thiazin-4-ones has been elaborated and described. The compounds were prepared by the reaction of aryl-modified sulfinylbis [(2,4-dihydroxyphenyl)methanethione]s and the corresponding aminothiophenecarboxamides. The derivatives showed anticancer activity in vitro. These compounds inhibited the proliferation and viability of lung cancer A549, colon cancer HT-29 and glioma C6 cells in a concentration-dependent manner. Some of the derivatives had no influence on normal skin fibroblasts culture viability. Moreover, one compound (1b) showed the ability to inhibit DNA synthesis in cancer cells, especially in C6 cells, and was not toxic for normal oligodendrocytes and hepatocytes. Using reversed phase RP 18 HPLC and immobilised artificial membrane (IAM) chromatography the phase affinity of the compounds was determined. The influence of lipophilicity on the activity of compounds has been discussed.

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Acknowledgments

This project was financed from the funds of the National Science Centre in Poland allocated on the basis of the decision number DEC-2011/01/B/NZ4/05005.

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Authors and Affiliations

  1. Department of Chemistry, University of Life Sciences in Lublin, 20-950, Lublin, Poland

    Joanna Matysiak, Alicja Skrzypek & Andrzej Niewiadomy

  2. Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090, Lublin, Poland

    Małgorzata Juszczak, Ewa Langner, Marta K. Lemieszek & Wojciech Rzeski

  3. Institute of Industrial Organic Chemistry in Warsaw, Annopol 6, 03-236, Warsaw, Poland

    Monika M. Karpińska & Andrzej Niewiadomy

  4. Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093, Lublin, Poland

    Ewa Langner & Katarzyna Walczak

  5. Department of Virology and Immunology, Maria Curie-Skłodowska University in Lublin, Akademicka 19, 20-033, Lublin, Poland

    Wojciech Rzeski

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  1. Joanna Matysiak
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Matysiak, J., Juszczak, M., Karpińska, M.M. et al. Synthesis of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-ones, their lipophilicity and anticancer activity in vitro. Mol Divers 19, 725–736 (2015). https://doi.org/10.1007/s11030-015-9599-x

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