Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity
Fluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had ob...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Journal of Saudi Chemical Society |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610324000486 |
| _version_ | 1797215979584880640 |
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| author | Yong Zhang Mei Zhu Kun Hu Xing Liu Yue Zou Jixiang Chen |
| author_facet | Yong Zhang Mei Zhu Kun Hu Xing Liu Yue Zou Jixiang Chen |
| author_sort | Yong Zhang |
| collection | DOAJ |
| description | Fluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had obvious antifungal activities against Phomopsis sp., among them, the EC50 value of compound C24 was 5.7 mg/L, which was significantly better than fluopyram (105.4 mg/L). The curative and protective activities of compound C24 on kiwi fruit infected with Phomopsis sp. were 42.2 and 52.9 %, which were better than that of fluopyram (30.4 and 35.6 %) at 200 mg/L. Moreover, compound C24 exhibited excellent inhibitory against SDH. The results of scanning electron microscopy (SEM) indicated that the mycelium of Phomopsis sp. collapsed or even ruptured after compound C24 treatment. Meanwhile, molecular docking showed that compound C24 was deeply embedded into the SDH binding pocket, and the binding model was stabilized by a cation–π interaction with Cys-40, Tyr-58 and an H-bond with Lys-455 and Asn-452. Compound C24 can provide a valuable idea to find new succinate dehydrogenase inhibitors. |
| first_indexed | 2024-04-24T11:38:40Z |
| format | Article |
| id | doaj.art-af9825dca5814b8fa3a6dcc8d3d17477 |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-04-24T11:38:40Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-af9825dca5814b8fa3a6dcc8d3d174772024-04-10T04:28:44ZengElsevierJournal of Saudi Chemical Society1319-61032024-05-01283101853Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivityYong Zhang0Mei Zhu1Kun Hu2Xing Liu3Yue Zou4Jixiang Chen5State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaState Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaState Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaState Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaState Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaCorresponding author.; State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, ChinaFluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had obvious antifungal activities against Phomopsis sp., among them, the EC50 value of compound C24 was 5.7 mg/L, which was significantly better than fluopyram (105.4 mg/L). The curative and protective activities of compound C24 on kiwi fruit infected with Phomopsis sp. were 42.2 and 52.9 %, which were better than that of fluopyram (30.4 and 35.6 %) at 200 mg/L. Moreover, compound C24 exhibited excellent inhibitory against SDH. The results of scanning electron microscopy (SEM) indicated that the mycelium of Phomopsis sp. collapsed or even ruptured after compound C24 treatment. Meanwhile, molecular docking showed that compound C24 was deeply embedded into the SDH binding pocket, and the binding model was stabilized by a cation–π interaction with Cys-40, Tyr-58 and an H-bond with Lys-455 and Asn-452. Compound C24 can provide a valuable idea to find new succinate dehydrogenase inhibitors.http://www.sciencedirect.com/science/article/pii/S1319610324000486Amide containing azetidineBioactivityMolecular dockingSDH inhibitor |
| spellingShingle | Yong Zhang Mei Zhu Kun Hu Xing Liu Yue Zou Jixiang Chen Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity Journal of Saudi Chemical Society Amide containing azetidine Bioactivity Molecular docking SDH inhibitor |
| title | Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity |
| title_full | Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity |
| title_fullStr | Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity |
| title_full_unstemmed | Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity |
| title_short | Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity |
| title_sort | novel amide derivatives containing azetidine moiety as potential sdh inhibitors design synthesis and evaluation of bioactivity |
| topic | Amide containing azetidine Bioactivity Molecular docking SDH inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S1319610324000486 |
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