Email this article Evaluation of N-Hydroxy-, N-Metoxy-, and N-Acetoxybenzoyl-Substituted Derivatives of Thymine and Uracil as New Substances for Prevention and Treatment of Long-Term Complications of Diabetes Mellitus
- Authors: Spasov A.A.1,2,3, Brel A.K.1, Litvinov R.A.1,3, Lisina S.V.1, Kucheryavenko A.F.1, Budaeva Y.N.1, Salaznikova O.A.1, Rashchenko A.I.1, Shamshina D.D.1, Batrakov V.V.1, Ivanov A.V.1
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Affiliations:
- Volgograd State Medical University
- Volgograd Medical Scientific Center
- Scientific Institute of Pharmacology of VSMU
- Issue: Vol 44, No 6 (2018)
- Pages: 769-777
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229151
- DOI: https://doi.org/10.1134/S1068162019010163
- ID: 229151
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Abstract
New uracil and thymine derivatives, N1-,N3- and N1,N3-(RO-benzoyl)-(1H,3H)-pyrimidine- 2,4-diones, were synthesized (RO- is hydroxy, acetoxy- or methoxy-group). The compounds were studied in a complex of in vitro tests for the ability to inhibit the development of long-term complications of diabetes. Their ability to cleave cross-links of proteins has been evaluated. The most significant ways of pharmacological correction of thrombosis, angio-, nephro-, encephalo-, and cardiopathy, antiglycation, chelating, and antiplatelet activities, have been established. The most active compound in terms of antiplatelet action, N1- hydroxybenzoyluracil, exceeded acetylsalicylic acid by ~44%. In terms of their ability to chelate copper (II) cations, all compounds (with the exception of 1,3-bis(3-hydroxybenzoyl)-(1H,3H)-pyrimidine-2,4-dione that was not not studied in this test) showed the activity, whose IC50 fell in the range between that for pioglitazone (44.1 μM) and pyridoxamine (136.7 μM) comparison drugs. The best antiglycation effect at the 1 mM concentration was observed for N1,N3-bismethoxy- and N1,N3-bisacetoxybenzoyl derivatives of thymine. The maximum activity to cleave cross-links of proteins (C = 1 mM), comparable to that of alagebrium, was established for 1,3-bis(4-methoxybenzoyl)uracil, for which also high rates of other estimated activities were noted. Thus, the N1-,N3- and N1,N3-(RO-benzoyl) derivatives of uracil and thymine are promising basiсs for creating drugs that suppress the development of long-term complications of diabetes.
About the authors
A. A. Spasov
Volgograd State Medical University; Volgograd Medical Scientific Center; Scientific Institute of Pharmacology of VSMU
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131; Volgograd, 400081; Volgograd, 400001
A. K. Brel
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
R. A. Litvinov
Volgograd State Medical University; Scientific Institute of Pharmacology of VSMU
Author for correspondence.
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131; Volgograd, 400001
S. V. Lisina
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
A. F. Kucheryavenko
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
Yu. N. Budaeva
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
O. A. Salaznikova
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
A. I. Rashchenko
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
D. D. Shamshina
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
V. V. Batrakov
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
A. V. Ivanov
Volgograd State Medical University
Email: litvinov.volggmu@mail.ru
Russian Federation, Volgograd, 400131
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