3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors
The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely use...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1174 |
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| author | Natalia A. Lozinskaya Elena N. Bezsonova Meriam Dubar Daria D. Melekhina Daniil R. Bazanov Alexander S. Bunev Olga B. Grigor’eva Vladlen G. Klochkov Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Sergey E. Sosonyuk |
| author_facet | Natalia A. Lozinskaya Elena N. Bezsonova Meriam Dubar Daria D. Melekhina Daniil R. Bazanov Alexander S. Bunev Olga B. Grigor’eva Vladlen G. Klochkov Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Sergey E. Sosonyuk |
| author_sort | Natalia A. Lozinskaya |
| collection | DOAJ |
| description | The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study of 3-arylidene-2-oxindoles as novel NRH:quinone oxidoreductase inhibitors. It was demonstrated that oxindoles with 6-membered aryls in the arylidene moiety were obtained predominantly as <i>E</i>-isomers while for some 5-membered aryls, the <i>Z</i>-isomers prevailed. The most active compounds inhibited NQO2 with an IC<sub>50</sub> of 0.368 µM. The presence of a double bond in the oxindoles was crucial for NQO2 inhibition activity. There was no correlation between NQO2 inhibition activity of the synthesized compounds and their cytotoxic effect on the A549 cell line. |
| first_indexed | 2024-03-11T09:33:54Z |
| format | Article |
| id | doaj.art-f853fec7228a4d49b587ac47a06f585a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:33:54Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f853fec7228a4d49b587ac47a06f585a2023-11-16T17:28:41ZengMDPI AGMolecules1420-30492023-01-01283117410.3390/molecules280311743-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 InhibitorsNatalia A. Lozinskaya0Elena N. Bezsonova1Meriam Dubar2Daria D. Melekhina3Daniil R. Bazanov4Alexander S. Bunev5Olga B. Grigor’eva6Vladlen G. Klochkov7Elena V. Sokolova8Denis A. Babkov9Alexander A. Spasov10Sergey E. Sosonyuk11Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaMedicinal Chemistry Center, Togliatti State University, 445020 Togliatti, RussiaMedicinal Chemistry Center, Togliatti State University, 445020 Togliatti, RussiaDepartment of Pharmacology & Bioinformatics, Volgograd State Medical University, 400131 Volgograd, RussiaDepartment of Pharmacology & Bioinformatics, Volgograd State Medical University, 400131 Volgograd, RussiaDepartment of Pharmacology & Bioinformatics, Volgograd State Medical University, 400131 Volgograd, RussiaDepartment of Pharmacology & Bioinformatics, Volgograd State Medical University, 400131 Volgograd, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaThe enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study of 3-arylidene-2-oxindoles as novel NRH:quinone oxidoreductase inhibitors. It was demonstrated that oxindoles with 6-membered aryls in the arylidene moiety were obtained predominantly as <i>E</i>-isomers while for some 5-membered aryls, the <i>Z</i>-isomers prevailed. The most active compounds inhibited NQO2 with an IC<sub>50</sub> of 0.368 µM. The presence of a double bond in the oxindoles was crucial for NQO2 inhibition activity. There was no correlation between NQO2 inhibition activity of the synthesized compounds and their cytotoxic effect on the A549 cell line.https://www.mdpi.com/1420-3049/28/3/1174oxindolesindolin-2-onesNQO2NRH:quinone oxidoreductase 23-arylidene-2-oxindolesanticancer |
| spellingShingle | Natalia A. Lozinskaya Elena N. Bezsonova Meriam Dubar Daria D. Melekhina Daniil R. Bazanov Alexander S. Bunev Olga B. Grigor’eva Vladlen G. Klochkov Elena V. Sokolova Denis A. Babkov Alexander A. Spasov Sergey E. Sosonyuk 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors Molecules oxindoles indolin-2-ones NQO2 NRH:quinone oxidoreductase 2 3-arylidene-2-oxindoles anticancer |
| title | 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors |
| title_full | 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors |
| title_fullStr | 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors |
| title_full_unstemmed | 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors |
| title_short | 3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors |
| title_sort | 3 arylidene 2 oxindoles as potent nrh quinone oxidoreductase 2 inhibitors |
| topic | oxindoles indolin-2-ones NQO2 NRH:quinone oxidoreductase 2 3-arylidene-2-oxindoles anticancer |
| url | https://www.mdpi.com/1420-3049/28/3/1174 |
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