In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans
Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century. Traditional methods, such as fungicides, have drawbacks including high cost, restrictions on organic farming, potential risks to the environment and human he...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-06-01
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| Series: | Advanced Agrochem |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773237124001023 |
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| author | Vasyl Kovalishyn Diana Hodyna Ivan Semenyuta Volodymyr Brovarets Oleh Shablykin Svitlana Chumachenko Larysa Metelytsia |
| author_facet | Vasyl Kovalishyn Diana Hodyna Ivan Semenyuta Volodymyr Brovarets Oleh Shablykin Svitlana Chumachenko Larysa Metelytsia |
| author_sort | Vasyl Kovalishyn |
| collection | DOAJ |
| description | Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century. Traditional methods, such as fungicides, have drawbacks including high cost, restrictions on organic farming, potential risks to the environment and human health, and the development of resistant strains. In this study, we employed cutting-edge computer-based techniques, including Quantitative Structure-Activity Relationship (QSAR) modeling and molecular docking simulations, to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P. infestans. QSAR modeling on the number of compounds tested as P. infestans inhibitors was performed using an interactive OCHEM web platform. The predictive ability of the developed classification models had a balanced accuracy (BA) of 77–85 % for the training set and BA = 89–93 % for the validation external test set. During the in vitro testing against P. infestans, thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates, ranging from 23.6 % to 87.4 %. The fungicidal potential of six of these fungicides ranged from 79.3 % to 87.4 %, which is comparable to the activity of known fungicides. Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d, 3f, 3h, 3j, 3k, and 3l, with LC50 values ranging from 13.7 to 52.9 mg/L, are low-toxicity compounds. The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51, a sterol biosynthesis enzyme. |
| format | Article |
| id | doaj-art-33aec16a4b8e4b2dbb14a5d0a16a8dbd |
| institution | OA Journals |
| issn | 2773-2371 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Advanced Agrochem |
| spelling | doaj-art-33aec16a4b8e4b2dbb14a5d0a16a8dbd2025-08-20T02:24:18ZengKeAi Communications Co., Ltd.Advanced Agrochem2773-23712025-06-014214114810.1016/j.aac.2024.11.005In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestansVasyl Kovalishyn0Diana Hodyna1Ivan Semenyuta2Volodymyr Brovarets3Oleh Shablykin4Svitlana Chumachenko5Larysa Metelytsia6Corresponding author.; V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkraineV.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, UkrainePhytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century. Traditional methods, such as fungicides, have drawbacks including high cost, restrictions on organic farming, potential risks to the environment and human health, and the development of resistant strains. In this study, we employed cutting-edge computer-based techniques, including Quantitative Structure-Activity Relationship (QSAR) modeling and molecular docking simulations, to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P. infestans. QSAR modeling on the number of compounds tested as P. infestans inhibitors was performed using an interactive OCHEM web platform. The predictive ability of the developed classification models had a balanced accuracy (BA) of 77–85 % for the training set and BA = 89–93 % for the validation external test set. During the in vitro testing against P. infestans, thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates, ranging from 23.6 % to 87.4 %. The fungicidal potential of six of these fungicides ranged from 79.3 % to 87.4 %, which is comparable to the activity of known fungicides. Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d, 3f, 3h, 3j, 3k, and 3l, with LC50 values ranging from 13.7 to 52.9 mg/L, are low-toxicity compounds. The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51, a sterol biosynthesis enzyme.http://www.sciencedirect.com/science/article/pii/S2773237124001023OxoimidazolidinesPhytophthora infestansAcute toxicityQSARDocking |
| spellingShingle | Vasyl Kovalishyn Diana Hodyna Ivan Semenyuta Volodymyr Brovarets Oleh Shablykin Svitlana Chumachenko Larysa Metelytsia In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans Advanced Agrochem Oxoimidazolidines Phytophthora infestans Acute toxicity QSAR Docking |
| title | In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans |
| title_full | In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans |
| title_fullStr | In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans |
| title_full_unstemmed | In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans |
| title_short | In silico modeling and experimental validation of 2-oxoimidazolidin-4-sulfonamides as low-toxicity fungicides against Phytophthora infestans |
| title_sort | in silico modeling and experimental validation of 2 oxoimidazolidin 4 sulfonamides as low toxicity fungicides against phytophthora infestans |
| topic | Oxoimidazolidines Phytophthora infestans Acute toxicity QSAR Docking |
| url | http://www.sciencedirect.com/science/article/pii/S2773237124001023 |
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