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Cytotoxicity Studies of 5-Arylaminouracil Derivatives

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Abstract

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). Cytotoxicity assessment by the standard MTT test showed that most of the compounds lack significant toxicity towards the above cells. However, 5-(4-isopropylphenylamine)uracil and 5‑(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect towards the GBM6138 cell line with half-maximal inhibitory concentrations (IC50) of 9 and 2.3 μM, respectively. Antitumor activity was for the first time demonstrated for compounds of this type and can serve as a starting point for further research.

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Funding

This work was supported by the Russian Science Foundation (project nos. 19-74-10048, https://rscf.ru/project/19-74-10048/, synthesis of 5-arylamino uridine derivatives and 23-64-10018, https://rscf.ru/project/23-64-10018/, cytotoxicity testing).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    V. A. Kezin, E. S. Matyugina, S. A. Surzhikov, A. A. Maslova, I. L. Karpenko, A. V. Ivanov, S. N. Kochetkov & A. L. Khandazhinskaya

  2. Volgograd State Medical University, 400131, Volgograd, Russia

    M. S. Novikov

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  1. V. A. Kezin
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  2. E. S. Matyugina
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Kezin, V.A., Matyugina, E.S., Surzhikov, S.A. et al. Cytotoxicity Studies of 5-Arylaminouracil Derivatives. Mol Biol 58, 328–335 (2024). https://doi.org/10.1134/S0026893324020079

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