Russian Journal of Bioorganic Chemistry p. 769 - 777 (2018)
Update date:2022-08-11
Topics:
Spasov
Brel
Litvinov
Lisina
Kucheryavenko
Budaeva, Yu. N.
Salaznikova
Rashchenko
Shamshina
Batrakov
Ivanov
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.
View MoreShenzhen JYMed Technology Co.,Ltd.
website:http://www.jymedtech.com
Contact:+86-755-26612112
Address:RM1-105, Shenzhen Bio-incubator Base, 10 Gaoxin C Avc 1st, Nanshan District, Shenzhen, GD, China, 518057
Hangzhou Share Chemical Co., Ltd
Contact:+86-57187093700
Address:Hang Xing Road
Nanjing Chemlin Chemical Co., Ltd.
website:http://www.echemlin.cn
Contact:+86-25-83697070
Address:Rm.902 Longyin Plaza, No. 217 Zhongshan Rd.(N) Nanjing 210009,China
Jewim Pharmaceutical (Shandong) Co., Ltd
Contact:+8615621883869
Address:山东省泰安市高新技术产业开发区配天门大街西首
Beijing Stable Chemcial Co.ltd
Contact:86-10-63785052
Address:A1301 Technological Edifice. No.4 FuFeng Road,FengTai District, Beijing. China
Doi:10.1016/j.electacta.2006.11.034
(2007)Doi:10.1021/jp970211z
(1997)Doi:10.1016/j.poly.2005.04.022
(2005)Doi:10.1016/j.molstruc.2019.04.074
()Doi:10.1039/b823467a
(2009)Doi:10.1039/c9dt01633c
(2019)