Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1
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 th...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/1422-8599/2023/4/M1743 |
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| author | Kseniya S. Kovaleva Olga I. Yarovaya Irina A. Chernyshova Alexandra L. Zakharenko Sergey V. Cheresiz Amirhossein Azimirad Andrey G. Pokrovsky Olga I. Lavrik Nariman F. Salakhutdinov |
| author_facet | Kseniya S. Kovaleva Olga I. Yarovaya Irina A. Chernyshova Alexandra L. Zakharenko Sergey V. Cheresiz Amirhossein Azimirad Andrey G. Pokrovsky Olga I. Lavrik Nariman F. Salakhutdinov |
| author_sort | Kseniya S. Kovaleva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T20:30:58Z |
| format | Article |
| id | doaj.art-762c351df9fd453b962ba98d14d82149 |
| institution | Directory Open Access Journal |
| issn | 1422-8599 |
| language | English |
| last_indexed | 2024-03-08T20:30:58Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molbank |
| spelling | doaj.art-762c351df9fd453b962ba98d14d821492023-12-22T14:27:04ZengMDPI AGMolbank1422-85992023-11-0120234M174310.3390/M1743Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1Kseniya S. Kovaleva0Olga I. Yarovaya1Irina A. Chernyshova2Alexandra L. Zakharenko3Sergey V. Cheresiz4Amirhossein Azimirad5Andrey G. Pokrovsky6Olga I. Lavrik7Nariman F. Salakhutdinov8N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, RussiaNovosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, RussiaNovosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, RussiaV. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, RussiaV. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, RussiaV. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, RussiaNovosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, RussiaNew 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.https://www.mdpi.com/1422-8599/2023/4/M1743resin acidsTDP1 inhibitorsheterocyclic compoundsDNA repairparabanic acidadamantane |
| spellingShingle | Kseniya S. Kovaleva Olga I. Yarovaya Irina A. Chernyshova Alexandra L. Zakharenko Sergey V. Cheresiz Amirhossein Azimirad Andrey G. Pokrovsky Olga I. Lavrik Nariman F. Salakhutdinov Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 Molbank resin acids TDP1 inhibitors heterocyclic compounds DNA repair parabanic acid adamantane |
| title | Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 |
| title_full | Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 |
| title_fullStr | Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 |
| title_full_unstemmed | Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 |
| title_short | Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1 |
| title_sort | synthesis of norabietyl and nordehydroabietyl imidazolidine 2 4 5 triones and their activity against tyrosyl dna phosphodiesterase 1 |
| topic | resin acids TDP1 inhibitors heterocyclic compounds DNA repair parabanic acid adamantane |
| url | https://www.mdpi.com/1422-8599/2023/4/M1743 |
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