Haolin Yuan, Hongwei Yang, Yang Gao, Jin Zhang, Jinzhou Ren, Xiaoyu Liu, Yixiao Li, Zhengming Li, Bin Zhao* and Zhijin Fan*,
{"title":"发现新型 Spiropiperidinyl-α-methylene-γ-butyrolactones 作为针对氧基甾醇结合蛋白的抗真菌和抗毒素药物。","authors":"Haolin Yuan, Hongwei Yang, Yang Gao, Jin Zhang, Jinzhou Ren, Xiaoyu Liu, Yixiao Li, Zhengming Li, Bin Zhao* and Zhijin Fan*, ","doi":"10.1021/acs.jafc.4c02848","DOIUrl":null,"url":null,"abstract":"<p >Corn ear rot and fumonisin caused by <i>Fusarium verticillioides</i> pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The <i>in vitro</i> bioassay results indicated that compound <b>7c</b> showed broad-spectrum <i>in vitro</i> activity with EC<sub>50</sub> values falling from 3.51 to 24.10 μg/mL against <i>Rhizoctonia solani</i> and <i>Alternaria solani</i>, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound <b>7c</b> also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both <b>7c</b> and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.</p>","PeriodicalId":41,"journal":{"name":"Journal of Agricultural and Food Chemistry","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery of Novel Spiropiperidinyl-α-methylene-γ-butyrolactones as Antifungal and Antitoxin Agents Targeting Oxysterol Binding Protein\",\"authors\":\"Haolin Yuan, Hongwei Yang, Yang Gao, Jin Zhang, Jinzhou Ren, Xiaoyu Liu, Yixiao Li, Zhengming Li, Bin Zhao* and Zhijin Fan*, \",\"doi\":\"10.1021/acs.jafc.4c02848\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Corn ear rot and fumonisin caused by <i>Fusarium verticillioides</i> pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The <i>in vitro</i> bioassay results indicated that compound <b>7c</b> showed broad-spectrum <i>in vitro</i> activity with EC<sub>50</sub> values falling from 3.51 to 24.10 μg/mL against <i>Rhizoctonia solani</i> and <i>Alternaria solani</i>, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound <b>7c</b> also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both <b>7c</b> and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.</p>\",\"PeriodicalId\":41,\"journal\":{\"name\":\"Journal of Agricultural and Food Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Agricultural and Food Chemistry\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jafc.4c02848\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"AGRICULTURE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Agricultural and Food Chemistry","FirstCategoryId":"97","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jafc.4c02848","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, MULTIDISCIPLINARY","Score":null,"Total":0}
Discovery of Novel Spiropiperidinyl-α-methylene-γ-butyrolactones as Antifungal and Antitoxin Agents Targeting Oxysterol Binding Protein
Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 μg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
期刊介绍:
The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.