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

A. A. Spasov; A. K. Brel; R. A. Litvinov; S. V. Lisina; A. F. Kucheryavenko; Yu. N. Budaeva; O. A. Salaznikova; A. I. Rashchenko; D. D. Shamshina; V. V. Batrakov; A. V. Ivanov

doi:10.1134/S1068162019010163

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

Autores: 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
Afiliações:
1. Volgograd State Medical University
2. Volgograd Medical Scientific Center
3. Scientific Institute of Pharmacology of VSMU
Edição: Volume 44, Nº 6 (2018)
Páginas: 769-777
Seção: Article
URL: https://journals.rcsi.science/1068-1620/article/view/229151
DOI: https://doi.org/10.1134/S1068162019010163
ID: 229151

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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.

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diabetes mellitus, long-term complications of diabetes mellitus, pyrimidine, thymine, uracil

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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

Texto integral

Resumo

Palavras-chave

Sobre autores

A. Spasov

A. Brel

R. Litvinov

S. Lisina

A. Kucheryavenko

Yu. Budaeva

O. Salaznikova

A. Rashchenko

D. Shamshina

V. Batrakov

A. Ivanov

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