Yuhao Zhang, Ruofei Bai, Tengyi Du, Yiwei Wang, Bohang Zhou, Congwei Zhou, Le Zhou
{"title":"针对植物病原真菌的 N-取代 N′-苯基吡啶肼的设计、合成、生物活性和作用机制","authors":"Yuhao Zhang, Ruofei Bai, Tengyi Du, Yiwei Wang, Bohang Zhou, Congwei Zhou, Le Zhou","doi":"10.1007/s11030-024-10984-9","DOIUrl":null,"url":null,"abstract":"<p><i>N</i>′-phenylpicolinohydrazide has been proven to be a promising lead compound for research and development of novel fungicides for agriculture in our previous study. As our continuing research, in this study, a series of <i>N</i>-substituted derivatives of <i>N</i>′-phenylpicolinohydrazide were synthesized and explored for the inhibition activity on nine phytopathogenic fungi and action mechanism. The results found that eleven of the compounds had excellent antifungal activity with more than 80% inhibition rates at 50 <i>µ</i>g/mL on part or most of the fungi, especially <i>A. solani</i> and <i>P. piricola</i>. Compounds <b>5i</b>, <b>5j</b> and <b>5k</b> showed EC<sub>50</sub> values of < 8.0 µg/mL against <i>A. solani</i> superior to positive control carbendazim (EC<sub>50</sub> = 36.0 µg/mL) while <b>5p</b> and <b>5q</b> exhibited the highest activity with EC<sub>50</sub> values of 2.72 and 2.80 µg/mL against <i>P. piricola</i> superior to positive control boscalid (EC<sub>50</sub> > 50.0 µg/mL). Furthermore, <b>5k</b> also showed significant protective effect against <i>A. solani</i> infection on tomatoes in a concentration-dependent manner. Action mechanism research showed that <b>5k</b> was able to increase the intracellular ROS level, change both MMP and permeability of cell membrane and damage mycelial morphology. Molecular docking studies showed that <b>5k</b> could bind into ubiquinone-binding region of succinate dehydrogenase by hydrogen bonds, π-cation, π–π stacked, π-alkyl, and alkyl interactions. Additionally, the antibacterial activity was also investigated. Thus, <i>N</i>-substituted derivatives of <i>N</i>′-phenylpicolinohydrazide were emerged as novel and highly promising antifungal molecular skeletons to develop new fungicides for crop protection.</p><h3 data-test=\"abstract-sub-heading\">Graphic abstract</h3>\n","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"23 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, bioactivity and action mechanism of N-substituted N′-phenylpicolinohydrazides against phytopathogenic fungi\",\"authors\":\"Yuhao Zhang, Ruofei Bai, Tengyi Du, Yiwei Wang, Bohang Zhou, Congwei Zhou, Le Zhou\",\"doi\":\"10.1007/s11030-024-10984-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>N</i>′-phenylpicolinohydrazide has been proven to be a promising lead compound for research and development of novel fungicides for agriculture in our previous study. As our continuing research, in this study, a series of <i>N</i>-substituted derivatives of <i>N</i>′-phenylpicolinohydrazide were synthesized and explored for the inhibition activity on nine phytopathogenic fungi and action mechanism. The results found that eleven of the compounds had excellent antifungal activity with more than 80% inhibition rates at 50 <i>µ</i>g/mL on part or most of the fungi, especially <i>A. solani</i> and <i>P. piricola</i>. Compounds <b>5i</b>, <b>5j</b> and <b>5k</b> showed EC<sub>50</sub> values of < 8.0 µg/mL against <i>A. solani</i> superior to positive control carbendazim (EC<sub>50</sub> = 36.0 µg/mL) while <b>5p</b> and <b>5q</b> exhibited the highest activity with EC<sub>50</sub> values of 2.72 and 2.80 µg/mL against <i>P. piricola</i> superior to positive control boscalid (EC<sub>50</sub> > 50.0 µg/mL). Furthermore, <b>5k</b> also showed significant protective effect against <i>A. solani</i> infection on tomatoes in a concentration-dependent manner. Action mechanism research showed that <b>5k</b> was able to increase the intracellular ROS level, change both MMP and permeability of cell membrane and damage mycelial morphology. Molecular docking studies showed that <b>5k</b> could bind into ubiquinone-binding region of succinate dehydrogenase by hydrogen bonds, π-cation, π–π stacked, π-alkyl, and alkyl interactions. Additionally, the antibacterial activity was also investigated. 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Design, synthesis, bioactivity and action mechanism of N-substituted N′-phenylpicolinohydrazides against phytopathogenic fungi
N′-phenylpicolinohydrazide has been proven to be a promising lead compound for research and development of novel fungicides for agriculture in our previous study. As our continuing research, in this study, a series of N-substituted derivatives of N′-phenylpicolinohydrazide were synthesized and explored for the inhibition activity on nine phytopathogenic fungi and action mechanism. The results found that eleven of the compounds had excellent antifungal activity with more than 80% inhibition rates at 50 µg/mL on part or most of the fungi, especially A. solani and P. piricola. Compounds 5i, 5j and 5k showed EC50 values of < 8.0 µg/mL against A. solani superior to positive control carbendazim (EC50 = 36.0 µg/mL) while 5p and 5q exhibited the highest activity with EC50 values of 2.72 and 2.80 µg/mL against P. piricola superior to positive control boscalid (EC50 > 50.0 µg/mL). Furthermore, 5k also showed significant protective effect against A. solani infection on tomatoes in a concentration-dependent manner. Action mechanism research showed that 5k was able to increase the intracellular ROS level, change both MMP and permeability of cell membrane and damage mycelial morphology. Molecular docking studies showed that 5k could bind into ubiquinone-binding region of succinate dehydrogenase by hydrogen bonds, π-cation, π–π stacked, π-alkyl, and alkyl interactions. Additionally, the antibacterial activity was also investigated. Thus, N-substituted derivatives of N′-phenylpicolinohydrazide were emerged as novel and highly promising antifungal molecular skeletons to develop new fungicides for crop protection.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;