Assessment of cytotoxicity of 5-arylaminouracil derivatives

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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. The cytotoxicity of 5-aminouracils with various substituents, as well as their 5’-norcabocyclic and ribo derivatives, was screened against two neuroblastoma cell lines (SH-SY5Y and IMR-32), lymphoblastic cells K-562, promyeoloblastic cells HL-60 and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). As a result of assessing the cytotoxicity of the resulting compounds on the above cell lines using the standard MTT test, it was revealed that most of the compounds do not have significant toxicity. However, in the GBM-6138 cell line, 5-(4-isopropylphenylamine)uracil and 5-(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect, with half-maximal inhibition concentrations IC50 of 9 μM and 2.3 μM, respectively. The antitumor activity of compounds of this type has been demonstrated for the first time and can serve as a starting point for further research.

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作者简介

V. Kezin

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

E. Matyugina

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

S. Surzhikov

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

M. Novikov

Volgograd State Medical University

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Volgograd, 400131

A. Maslova

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

I. Karpenko

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

A. Ivanov

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

S. Kochetkov

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

A. Khandazhinskaya

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

编辑信件的主要联系方式.
Email: khandazhinskaya@bk.ru
俄罗斯联邦, Moscow, 119991

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2. Fig. 1. Structure of 5-aminouracil molecules (1a-e), their 5’-norcabocyclic (2a-e) and ribo derivatives (3a-e).

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3. Scheme 1. Reaction conditions. i: 5-R-persilylated uracil, TMCSiTfl, 1,2-dichloroethane, ii: NH4OH/EtOH.

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