Copyright: © 2026 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).
ORIGINAL RESEARCH
The structure and biological potential of substituted uracil-propanesultone derivatives: from tautomeric preferences to drug design
About authors
1 Pirogov Russian National Research Medical University, Moscow, Russia
2 Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Moscow, Russia
Correspondence should be addressed: Vadim V. Negrebetsky
Ostrovityanova Str., 1, Moscow, 117513, Russia; ur.umsr@1ykstebergen
About paper
Author contribution: Gusev RA — performing QSAR analysis, preparation of the manuscript; Kramarova EP — preparation of the manuscript; Volchenkov TI — performing QSAR analysis; Korlyukov AA — quantum-chemical calculations, preparation of the manuscript; Lagunin AA — performing QSAR analysis, preparation of the manuscript; Baukov YI — academic advising; Shmigol TA — biological part, preparation of the manuscript; Negrebetsky VV — formulation of the study goal, preparation of the manuscript; all authors contributed equally to the preparation of the manuscript; they confirm that their contribution complies with the international criteria of ICMJE.
Received: 2026-05-29
Accepted: 2026-06-10
Published online: 2026-06-16
|
A comprehensive study of 10 N-sulfopropylated uracil derivatives (7–16), differing in substituents at positions C(5) and C(6) (H, CH3, NO2, Br, Cl, I, NH2), including 36 possible tautomeric forms, was carried out using methods of quantum chemistry (ωB97X-3c, CPCM) and prediction of the spectrum of biological activity in silico (PASS and PharmaExpert programs, version 2024). In every case, diketo-tautomer a is the dominant form in the condensed phase (ΔΔG=0). Depending on the substituent, the relative Gibbs energy values for keto-enol tautomers b and c range from 36 to 122 kJ/mol. It has been shown that the introduction of a sulfopropyl group does not violate the tautomeric preferences of unsubstituted uracil. A wide range of biological activity of the investigated structures was predicted using QSAR analysis. Antiviral effects (including HIV activity), antibacterial effects, anti-ischemic activity, and neuroprotective effects associated with inhibition of beta-amyloid aggregation were the most highly anticipated outcomes. The potential risks of hemotoxicity and peripheral neuropathy for nitro derivatives have been revealed (9). Diketo forms of N-sulfopropylated uracils with moderate electron-donor substituents are promising candidates for the development of multitargeted neuroprotective and antiviral drugs.
Keywords: antiviral activity, neuroprotection, uracil, N-sulfoalkylation, 1, 3-propane sultone, tautomerism, diketo form, DFT, QSAR, β-amyloid inhibition