Cytotoxicity Studies of 5-Arylaminouracil Derivatives

• Published in: Molecular biology (New York) Vol. 58; no. 2; pp. 328 - 335
• Main Authors: Kezin, V. A., Matyugina, E. S., Surzhikov, S. A., Novikov, M. S., Maslova, A. A., Karpenko, I. L., Ivanov, A. V., Kochetkov, S. N., Khandazhinskaya, A. L.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-04-2024; Springer Nature B.V
• Subjects: Antitumor activity; Biochemistry; Biomedical and Life Sciences; Brain tumors; Cell differentiation; Cytotoxicity; Glioblastoma; Glioma; Herpes viruses; HIV; Human Genetics; Human immunodeficiency virus; Life Sciences; Neuronal-glial interactions; Structural-Functional Analysis of Biopolymers and Their Complexes; Uracil; synthesis; neuroblastoma; leukemia; glioma; antitumor activity; uracil derivatives
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893324020079

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 (IC
50
) 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.