Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1

被引:2
|
作者
Kovaleva, Kseniya S. [1 ]
Yarovaya, Olga I. [1 ]
Chernyshova, Irina A. [2 ]
Zakharenko, Alexandra L. [2 ]
Cheresiz, Sergey V. [3 ]
Azimirad, Amirhossein [3 ]
Pokrovsky, Andrey G. [3 ]
Lavrik, Olga I. [2 ]
Salakhutdinov, Nariman F. [1 ]
机构
[1] Russian Acad Sci, N N Vorozhtsov Novosibirsk Inst Organ Chem, Siberian Branch, Lavrentiev Ave 9, Novosibirsk 630090, Russia
[2] Russian Acad Sci, Novosibirsk Inst Chem Biol & Fundamental Med, Siberian Branch, Lavrentiev Ave 8, Novosibirsk 630090, Russia
[3] Novosibirsk State Univ, V Zelman Inst Med & Psychol, Pirogova St 1, Novosibirsk 630090, Russia
基金
俄罗斯科学基金会;
关键词
resin acids; TDP1; inhibitors; heterocyclic compounds; DNA repair; parabanic acid; adamantane; dehydroabietic acid; abietic acid; TDP1; INHIBITORS;
D O I
10.3390/M1743
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
New imidazolidine-2,4,5-triones with norabietic, nordehydroabietic, and adamantane substituents were synthesized by reacting oxalyl chloride and the corresponding ureas, providing good yields. Bioisosteric replacement of the ureide group with a parabanic acid fragment made it possible to increase the solubility of compounds and conduct biological studies. The compounds inhibit the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 in submicromolar concentrations. Cytotoxic concentrations were also studied on the glioblastoma cell line SNB19.
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页数:8
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