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Substituted N-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro

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Abstract

A library of hybrid molecules bearing thioglycoluril and (hetero)aromatic aldehyde thiosemicarbazone moieties was synthesized via a tandem hydrazone formation—ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (hetero)aromatic aldehydes. All synthesized compounds were tested for their cytotoxic activity against rhabdomyosarcoma, A549, and MS human cancer cell lines by MTT-assay. Among the derivatives, (E)-4-benzylideneamino-1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines (1f: IC\(_{50}= 20.6,\) 23.7, and 6.4 \(\upmu \)M, respectively). The IC\(_{50}\) value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 \(\upmu \)M, which appeared to be 3–11-fold higher than IC\(_{50}\) values of 1f against human cancer cells.

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Acknowledgments

High-resolution mass spectra were recorded in the Department of Structural Studies of N.D. Zelinsky Institute of Organic Chemistry, Moscow. This work was financially supported by the Russian Foundation for Basic Research (Projects No. 14-03-00556).

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Authors and Affiliations

  1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation

    Galina A. Gazieva, Tatyana B. Karpova & Angelina N. Kravchenko

  2. Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russian Federation

    Lada V. Anikina & Sergei A. Pukhov

  3. A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russian Federation

    Yulia V. Nelyubina

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  1. Galina A. Gazieva
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  2. Lada V. Anikina
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  3. Sergei A. Pukhov
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  4. Tatyana B. Karpova
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  5. Yulia V. Nelyubina
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  6. Angelina N. Kravchenko
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Correspondence to Galina A. Gazieva.

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Gazieva, G.A., Anikina, L.V., Pukhov, S.A. et al. Substituted N-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro. Mol Divers 20, 837–846 (2016). https://doi.org/10.1007/s11030-016-9671-1

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