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Efficient synthesis and evaluation of antiviral and antitumor activity of novel 3-phosphonylated thiazolo[3,2-a]oxopyrimidines

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Abstract

A series of 3-phosphonylated thiazolo[3,2-a]oxopyrimidines 3a-k was synthesized for the first time by the reactions of chloroethynylphosphonates with 5,6-disubstituted 2-thiouracils. In vitro antiviral activities have shown that the compounds 1i, 1j, 3b and 3e were shown activity against influenza A virus. In vitro antitumor activity was conducted for all compounds against human erythroleukemia (K562) and cervical carcinoma (HeLa) cell lines by MTS assay. Among targeted compounds 3c, 3h and 3j were active against human erythroleukemia (K562) cell line, while 3c and 3j were active against cervical carcinoma (HeLa) cell line. It was discovered that HeLa cells after treatment with compounds 3c and 3j significantly reduced the number of cells with stress fibers and with filopodium-like membrane protrusions. It was concluded that targeted compounds have a cytostatic effect, which could lead to a decrease in the formation of actin filaments and also in the number of filopodium-like membrane protrusions.

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Acknowledgements

We gratefully acknowledge the financial support from the Russian Foundation for Basic Research (Grant no. 19-03-00365) and the Ministry of Education and Science of the Russian Federation (0791-2020-0006). This research made use of resources from the Engineering Centre of Saint-Petersburg State Institute of Technology, the Centre for Chemical Analysis and Materials, and the Center for X-ray Diffraction Methods of Saint-Petersburg State University.

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Authors and Affiliations

  1. Institute of Chemistry, St. Petersburg State University, 7/9 University Embankment, St. Petersburg, 199034, Russia

    Anastasia A. Babushkina

  2. Department of Organic Chemistry, St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013, Russia

    Albina V. Dogadina, Dmitrij M. Egorov & Julia L. Piterskaia

  3. Smorodintsev Research Institute of Influenza, prof. Popov str. 15/17, St. Petersburg, 197376, Russia

    Anna A. Shtro, Yulia V. Nikolaeva & Anastasia V. Galochkina

  4. Saint Petersburg National Research Academic University of the Russian Academy of Sciences, Khlopina str. 8/3, St. Petersburg, 194021, Russia

    Anton A. Kornev & Vitali M. Boitsov

  5. Pavlov First Saint Petersburg State Medical University, L’va Tolstogo str. 6-8, St. Petersburg, 197022, Russia

    Vitali M. Boitsov

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  1. Anastasia A. Babushkina
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Babushkina, A.A., Dogadina, A.V., Egorov, D.M. et al. Efficient synthesis and evaluation of antiviral and antitumor activity of novel 3-phosphonylated thiazolo[3,2-a]oxopyrimidines. Med Chem Res 30, 2203–2215 (2021). https://doi.org/10.1007/s00044-021-02801-x

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