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Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control

[Image: see text] Developing new fungicides is always crucial to protecting crops. A series of 4-(3,4-dichloroisothiazol-5-yl)-7-(2-((5-(5-pyrimidin-4-yl)amino)ethoxy)-8-methyl) coumarin derivatives were designed and synthesized by Williamson ether condensation and substitution reactions. Structure...

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Autores principales: Li, Kun, Li, Mengyuan, Zhong, Haolin, Tang, Liangfu, Lv, You, Fan, Zhijin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568580/
https://www.ncbi.nlm.nih.gov/pubmed/37841179
http://dx.doi.org/10.1021/acsomega.3c05734
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author Li, Kun
Li, Mengyuan
Zhong, Haolin
Tang, Liangfu
Lv, You
Fan, Zhijin
author_facet Li, Kun
Li, Mengyuan
Zhong, Haolin
Tang, Liangfu
Lv, You
Fan, Zhijin
author_sort Li, Kun
collection PubMed
description [Image: see text] Developing new fungicides is always crucial to protecting crops. A series of 4-(3,4-dichloroisothiazol-5-yl)-7-(2-((5-(5-pyrimidin-4-yl)amino)ethoxy)-8-methyl) coumarin derivatives were designed and synthesized by Williamson ether condensation and substitution reactions. Structure determinations were clarified by (1)H NMR, (13)C NMR, and HRMS, and compound 4h crystallized by the fusion method for further structural confirmation. The in vitro bioassay results showed that the target compounds displayed good fungicidal activity against Alternaria solani, Botrytis cinerea, Cercospora arachidicola, Fusarium graminearum, Physalospora piricola, Rhizoctonia solani, and Sclerotinia sclerotiorum. Among them, compounds 4b and 4d showed higher inhibitory activity against R. solani, with EC(50) values of 11.3 and 13.7 μg/mL, respectively, and they were more active than the positive control diflumetorim with an EC(50) value of 19.8 μg/mL. Molecular docking suggested that compound 4b and diflumetorim may have similar interactions with complex I NADH oxidoreductase. Density functional theory calculation and pesticide-likeness analysis studies gave a rational explanation of their fungicidal activity. These results indicated that compounds 4b and 4d deserved further optimization according to the principle of pesticide-likeness.
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spelling pubmed-105685802023-10-13 Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control Li, Kun Li, Mengyuan Zhong, Haolin Tang, Liangfu Lv, You Fan, Zhijin ACS Omega [Image: see text] Developing new fungicides is always crucial to protecting crops. A series of 4-(3,4-dichloroisothiazol-5-yl)-7-(2-((5-(5-pyrimidin-4-yl)amino)ethoxy)-8-methyl) coumarin derivatives were designed and synthesized by Williamson ether condensation and substitution reactions. Structure determinations were clarified by (1)H NMR, (13)C NMR, and HRMS, and compound 4h crystallized by the fusion method for further structural confirmation. The in vitro bioassay results showed that the target compounds displayed good fungicidal activity against Alternaria solani, Botrytis cinerea, Cercospora arachidicola, Fusarium graminearum, Physalospora piricola, Rhizoctonia solani, and Sclerotinia sclerotiorum. Among them, compounds 4b and 4d showed higher inhibitory activity against R. solani, with EC(50) values of 11.3 and 13.7 μg/mL, respectively, and they were more active than the positive control diflumetorim with an EC(50) value of 19.8 μg/mL. Molecular docking suggested that compound 4b and diflumetorim may have similar interactions with complex I NADH oxidoreductase. Density functional theory calculation and pesticide-likeness analysis studies gave a rational explanation of their fungicidal activity. These results indicated that compounds 4b and 4d deserved further optimization according to the principle of pesticide-likeness. American Chemical Society 2023-09-28 /pmc/articles/PMC10568580/ /pubmed/37841179 http://dx.doi.org/10.1021/acsomega.3c05734 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Li, Kun
Li, Mengyuan
Zhong, Haolin
Tang, Liangfu
Lv, You
Fan, Zhijin
Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title_full Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title_fullStr Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title_full_unstemmed Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title_short Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control
title_sort design and synthesis of pyrimidine amine containing isothiazole coumarins for fungal control
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568580/
https://www.ncbi.nlm.nih.gov/pubmed/37841179
http://dx.doi.org/10.1021/acsomega.3c05734
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