[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

Approximately 1,3-Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with promising anticancer activity. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were first investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using the recently proposed diffusion mixing technique, which led to ~5–15% increases in target compound yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance with the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in the nitrile imine structure and was significantly decreased in reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

Authors
Kuznetsova Juliana V.1 , Tkachenko Varvara T.1 , Petrovskaya Lada M.1 , Filkina Maria E.1 , Shybanov Dmitry E.1 , Grishin Yuri K.1 , Roznyatovsky Vitaly A.1 , Tafeenko Viktor A.1 , Pestretsova Anna S. 2, 3 , Yakovleva Vera A. 4 , Pokrovsky Vadim S. 2, 4, 5 , Kukushkin Maxim E.1 , Beloglazkina Elena K.1
Publisher
MDPI AG
Number of issue
1
Language
English
Pages
18
Status
Published
Volume
25
Year
2024
Organizations
  • 1 Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
  • 2 Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia
  • 3 Occupational Health Risks Lab, Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia
  • 4 Department of Biochemistry, People’s Friendship University of Russia (RUDN University), 117198 Moscow, Russia
  • 5 Research Institute of Molecular and Cellular Medicine, People’s Friendship University of Russia (RUDN University), 117198 Moscow, Russia
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