戊唑醇的作用特点及其应用概况

甾醇类化合物是生物维持生命及生长发育不可缺少的物质。在真菌和细菌中 ,主要是合成麦角甾醇 ,它是构成细胞膜的重要成分 ,对细胞膜的渗透性起重要作用。麦角甾醇的生物合成已成为新型杀菌剂的重要靶标之一 ,其抑制剂由于活性高、不易产生抗药性等特点 ,而在应用初期受到普遍重视。从化学结构来看 ,目前已开发出具有实用价值的品种主要是三唑类、咪唑类、吡啶类、吗啉类和哌嗪类等化合物。戊唑醇 (ｔｅｂｕｃｏｎａｚｏｌｅ)是一种羟乙基三唑衍生物 ,属三唑类内吸杀菌剂。毒性分类属低毒杀菌剂。该化合物由德国拜耳公司于１９８６年最先开…     

山西省清徐县葡萄霜霉菌对烯酰吗啉的抗药性分析

葡萄霜霉病是葡萄最重要的病害之一,目前防治霜霉病主要依赖化学药剂,其中羧酸酰胺类杀菌剂是一类重要药剂,然而病原菌抗药性对其防效有重要影响。2015年本实验室首次在中国检测到抗烯酰吗啉的葡萄霜霉菌,并开发了Tetra-Primer ARMS PCR快速检测法来检测抗药性。本研究利用此技术对采自山西省清徐县60株葡萄霜霉菌进行了烯酰吗啉抗性检测,结果显示其中1株具有抗药性,其他59株均为敏感菌株,说明该地区霜霉菌已经开始产生烯酰吗啉抗性,但尚未大范围扩展,需要进行持续监测以指导杀菌剂的使用,这也是首次报道山西省葡萄霜霉菌存在烯酰吗啉抗性菌株。     

双炔酰菌胺对辣椒疫病的作用方式及其持效期

辣椒疫病是由辣椒疫霉菌Phytophthora capsici引起的重要病害。目前,辣椒疫病仍以化学防治为主。甲霜灵等苯酰胺类杀菌剂的广泛使用,对防治辣椒疫病发挥了重要作用,但由于连年多次的使用致使不同地区辣椒疫霉菌对苯酰胺类杀菌剂均产生了一定程度的抗药性[1],因此寻求对辣椒疫病具有较好防治效果的新型杀菌剂已成为当务之急。双炔酰菌胺是由瑞士先正达公司开发的一种新型的羧酸酰胺类杀菌剂[2],国内尚未见使用双炔酰菌胺防治辣椒疫病的相关报道,为此,本试验就双炔酰菌胺对辣椒疫病的作用方式及持效期进行了研究,以期为该药剂在生产中的合理应用提供理论依据。     

杀菌剂氟苯醚酰胺的创制

琥珀酸脱氢酶 (succinate dehydrogenase, SDH) 是重要的杀菌剂靶标之一,而很多植物病原菌对靶向SDH的杀菌剂已经产生了较为严重的抗药性,因此新型靶向SDH的杀菌剂设计显得尤为重要。基于药效团连接碎片的虚拟筛选 (PFVS) 是一种独立于生物物理技术的高通量药物发现方法,采用PFVS方法成功获得了靶向SDH的新型杀菌剂候选化合物—氟苯醚酰胺。本文主要从PFVS原理、先导化合物的发现、取代基的修饰以及杀菌活性研究等方面对氟苯醚酰胺的创制进行系统分析。氟苯醚酰胺创制的案例分析可为农药研究工作者提供新思路和新方法。     

病菌抗药性的发生、检测和预防

近十几年来,随着各类内吸杀菌剂的广泛应用,病菌抗药性已成为农业生产中急待研究解决的问题。 一、抗药性的发生 内吸杀菌剂一般具有效力高、残效期长、选择性强、施药方法多样等优点,是杀菌剂发展的一个重要方向。继苯并眯唑类(如苯来特、多菌灵、甲基托布津)、丁烯酰胺     

拌种灵、叶枯唑和萎锈灵对病菌的毒力机制比较

苯氨基甲酰类杀菌剂是最早开发的一类内吸性杀菌剂 [1 ] ,能有效地防治一些真菌病害 ,持效性长 ,抗药性风险低 [2 ] 。对叶枯唑产生抗药性的水稻白叶枯病菌 ( Xanthomonas oryzae pv.oryzae)对拌种灵同样具有抗药性 [3] 。近年来 ,拌种灵被有效地用于防治果园中柑桔溃疡病 ( X.citri) [4]。目前对噻唑类杀菌剂防治细菌病害的作用机制尚不清楚 ,初步认为这类药剂最初的作用靶点可能与致病性相关因子有关 [3] 。我们对 3种具有相似结构的杀菌剂拌种灵、叶枯唑和萎锈灵在离体条件下对病原菌的毒力机制进行了初步研究 ,同时也对拌种灵防治柑桔…     

植物病原菌抗药性遗传研究

 植物病原菌对杀菌剂的抗药性是由遗传基因控制的,抗药基因位于细胞质遗传因子或细胞核染色体基因上,细菌对许多药剂如铜制剂、链霉素等的抗药性和真菌对少数药剂如甲氧丙烯酸酯类药剂的抗性属于前一种情况,而真菌对大多数药剂的抗性则属于后一种情况。核基因控制的抗药性又可分为主效基因(major-gene)抗性和微效多基因(poly-gene)抗性,分别使病菌对药剂的抗性表现质量性状和数量性状。病原菌对苯并咪唑类药剂、春日霉素、羧基酰胺类药剂、苯酰胺类药剂、芳烃类药剂、二甲酰亚胺类药剂等的抗性通常为主效基因控制;使病菌表现微效多基因抗性的杀菌剂主要有多果定、羟基嘧啶类药剂、甾醇合成抑制剂(SBIs)等     

吩嗪-1-羧酸双酰肼衍生物的合成、杀菌活性及韧皮部的输导性研究

天然产物吩嗪-1-羧酸（PCA，申嗪霉素）及其衍生物吩嗪-1-甲酰肼具有独特的化学结构和优良的杀菌等生物活性，但均没有韧皮部输导性。本文以具有抑菌活性的吩嗪-1-羧酸和具有韧皮部输导性的马来酰肼为先导化合物，将马来酰肼中的双酰肼结构引入到吩嗪-1-羧酸中，设计、合成了17个新化合物，其结构均经过核磁共振氢谱、高分辨质谱及X-射线单晶衍射分析确证。初步生物活性测试表明:大部分目标化合物在50 mg/L下对水稻纹枯病菌Thanatephorus cucumeris表现出中等偏上的抑制活性，其中化合物6m的抑制率达92%。但输导性研究结果显示，目标化合物没有明显的韧皮部输导性。     

五种琥珀酸脱氢酶抑制剂类杀菌剂与灰葡萄孢琥珀酸脱氢酶的结合模式及抗性机制分析

为探究琥珀酸脱氢酶抑制剂 (SDHI) 类杀菌剂与灰葡萄孢Botrytis cinerea琥珀酸脱氢酶 (SDH) (以下简称BcSDH) 的结合方式,阐明BcSDH对SDHI类杀菌剂产生抗性的结构生物学机制,通过同源建模构建了BcSDH的三维模型,通过分子对接预测了5种SDHI (异丙噻菌胺、氟吡菌酰胺、氟唑菌酰胺、吡噻菌胺和啶酰菌胺) 与野生型和突变型BcSDH的亲和力及结合模式之间的变化,分析其抗药性机制,对相关突变位点进行保守性预测,并分析突变类型。结果表明:5种SDHI与BcSDH 具有较强的亲和力,其中酸部分插入BcSDH活性腔底,胺部分在活性腔口,能够形成牢固的疏水作用、氢键、卤键、π-π堆积作用和π-阳离子等相互作用。B-P225F氨基酸残基突变 (以下简称突变) 会造成活性腔口变窄,使得SDHI酸部分不能进入活性腔;B-P225L突变会造成异丙噻菌胺、氟吡菌酰胺和吡噻菌胺与靶标蛋白的结合模式发生变化,亲和力降低;B-H272R突变后,活性腔底变窄,与SDHI的亲和力下降。另外,保守性分析结果表明,B-P225和B-H272均位于BcSDH的保守区域,B-P225F、B-H272R和B-H272L突变可能为随机突变。因此推测BcSDH的B-P225F和B-H272R突变可能是引起灰葡萄孢对5种杀菌剂产生抗性的主要原因,也可能是引起SDHI类杀菌剂之间交互抗性的主要原因之一;B-P225L突变可能降低灰葡萄孢对部分杀菌剂的敏感性,而不是引起BcSDH对SDHI类杀菌剂产生交互抗性的主要原因。在实际生产中,应采取合理有效的抗性监测治理策略来延缓灰葡萄孢对SDHI类杀菌剂抗性的产生,在SDHI分子设计时也应考虑该位点氨基酸残基突变,避免产生交互抗性。     

三种羧酸酰胺类杀菌剂对黄瓜疫霉菌不同发育阶段的影响及其敏感性测定

离体条件下测定了3种羧酸酰胺类(Carboxylic acid amides,CAAs)杀菌剂氟吗啉、烯酰吗啉和异丙菌胺对黄瓜疫霉菌不同生长发育阶段的抑制作用。结果表明,3种杀菌剂抑制黄瓜疫霉菌休止孢萌发的EC50值分别为0.54,0.46和 0.34 μg/mL;抑制菌丝生长的EC50值分别为0.92,0.70和0.67 μg/mL;抑制孢子囊形成的EC50值分别为0.48,0.31和0.26 μg/mL。但对游动孢子的释放、游动及休止孢的形成均没有抑制作用。氟吗啉、烯酰吗啉和异丙菌胺抑制田间采集的供试菌株菌丝生长的平均EC50值分别为1.09(±0.24),0.29(±0.04)和0.32 (±0.07) μg/mL,供试菌株对3种杀菌剂的敏感性均呈正态分布,未检测到抗药性菌株的存在。     

吡啶衍生物研究(IX):N-(1-甲氧羰基)乙基-N-[5-(2-氯吡啶-4-基)-1,3,4-噻二唑-2-基]酰胺的合成及除草活性

为了进一步研究前期发现的除草先导化合物2-仲丁氨基-5-(2-氯吡啶-4-基)-1，3，4-噻二唑(BCPT)的结构-活性关系并提高其除草活性，设计并合成了一系列N-(1-甲氧羰基)乙基-N-[5-(2-氯吡啶-4-基)-1，3，4-噻二唑-2-基]酰胺类化合物。其苗后除草活性测定结果表明，所有化合物的活性都远低于BCPT本身。说明BCPT可能具有与传统酰胺类除草剂不同的作用机制。     

含单萜酚结构酰胺类杂合分子的设计与合成及抑菌活性

为寻找具有良好抑菌活性的酰胺类化合物,本研究将天然单萜酚类化合物香芹酚和百里香酚与琥珀酸脱氢酶抑制剂(SDHI)药效团拼合,设计并合成了30个酰胺类杂合分子,其结构经核磁共振氢谱(1H NMR)、碳谱(13C NMR)及高分辨质谱(HRMS)等确认。采用菌丝生长速率法测定了目标化合物对5种植物病原真菌的抑菌活性。结果表明,目标化合物对茄链格孢菌Alternaria solani和灰葡萄孢Botrytis cinerea的抑菌活性较好,其中 7e (N-(4-羟基-5-异丙基-2-甲基苯)-3-甲基噻吩-2-酰胺)的活性最高,对茄链格孢菌和灰葡萄孢的EC₅₀值分别为3.28和15.06 μg/mL,且 7e 与啶酰菌胺之间没有交互抗性。琥珀酸脱氢酶(SDH)活性测定表明, 7e 对灰葡萄孢敏感、抗性和B-P225F突变菌株的SDH均具有较强的抑制活性。分子对接研究表明, 7e 与野生型和突变型灰葡萄孢琥珀酸脱氢酶(BcSDH)之间具有较强的亲和力;推测 7e 是潜在的新型SDHI,其与啶酰菌胺之间对菌株SDH抑制活性的差异和与野生型和突变型BcSDH之间结合模式的差异,可能是二者之间没有交互抗性的原因。     

几种化学物质诱导彩色马蹄莲对软腐病抗性的研究

本试验测定了纳米硅、草酸、硅酸钠和硫酸亚铁4种化学物质在不同浓度下对彩色马蹄莲软腐病菌的室内抑菌活性和诱导抗病效果。结果表明,硫酸亚铁3种浓度对彩色马蹄莲软腐病菌均表现较强的抑制作用;1 g/L纳米硅、0.15 g/L草酸和0.2 g/L硅酸钠3种化学物质对软腐病菌无明显抑制作用且诱导抗病效果较好,分别达到62.28%、77.56%、88.46%;经3种化学物质诱导处理后再进行接种,诱导处理和接种期间彩色马蹄莲叶片组织内过氧化物酶(POD)、苯丙氨酸解氨酶(PAL)、多酚氧化酶(PPO)酶活性均高于对照,其中硅酸钠处理后彩色马蹄莲叶片组织内POD、PAL活性高于纳米硅和草酸处理,草酸处理后叶片组织内PPO活性高于纳米硅和硅酸钠处理。     

Activity and metabolism of cyano-oxime derivatives in various strains of Botrytis cinerea

The fungitoxicity of cymoxanil, 4 cyano-oxime analogs (in which the acetylurea group was replaced with various groups: amide, ester, propargyl, and cyanomethyl-amide), and 2 cymoxanil-metabolites was studied against various strains of Botrytis cinerea. The fungicidal effect was measured on germ-tube elongation and mycelial growth. Cymoxanil and the analogs bearing the amide and ester groups showed the best anti-botrytis activity. The strains studied can be classified into 3 groups according to the germ-tube sensitivity to cyano-oximes. These groups fitted well with the 3 phenotypes of sensitivity to cymoxanil previously characterized in our laboratory: CyaS₁ (highly sensitive phenotype); CyaS₂ (moderately sensitive phenotype); and CyaR (tolerant phenotype). The bio-transformations of all the cyano-oximes were monitored in the culture-medium of the different strains using HPLC- and IP-HPTLC-methods. HPLC-studies showed that cymoxanil and the analogs bearing the groups amide and ester were quickly metabolized in the culture-medium of the CyaS₁ strain. Moreover, these studies allowed us to correlate disappearance of these cyano-oximes, to their fungicidal activity towards the CyaS₁ strain. This suggests that cyano-oximes and particularly cymoxanil are probably activated in a fungitoxic compound. IP-HPTLC-studies strengthened the precedent results and allowed us to correlate disappearance of cyano-oximes studied with appearance of two acids metabolites of hydrolysis. These metabolites could be the actual active-principles.     

Design, synthesis, insecticidal activity and structure-activity relationship of 3,3-dichloro-2-propenyloxy-containing phthalic acid diamide structures

BACKGROUND: Phthalic acid diamide derivatives are among the most important classes of synthetic insecticides. In this study, a 3,3‐dichloro‐2‐propenyloxy group, the essential active group of pyridalyl derivatives, was incorporated into phthalic acid diamide derivatives with the aim of combining the active groups to generate more potent insecticides. RESULTS: Thirty‐one new phthalic acid diamides were obtained, and these were characterised by ¹H and ¹³C NMR. The structure of N²‐[1,1‐dimethyl‐2‐(methoxy)ethyl]‐3‐iodo‐N¹‐[4‐(3,3‐dichloro‐2‐propenyloxy)‐3‐(trifluoromethyl)phenyl]‐1,2‐benzenedicarboxamide was determined by X‐ray diffraction crystallography. The insecticidal activities of the compounds against Plutella xylostella were evaluated. The title compounds exhibited excellent larvicidal activities against P. xylostella. Structure‐activity relationships revealed that varying the combination of aliphatic amide and aromatic amide moieties, or the nature and position of substituent Y on the aniline ring, could aid the design of structures with superior performance. CONCLUSION: A series of novel phthalic acid diamides containing a 3,3‐dichloro‐2‐propenyloxy group at the 4‐position of the aniline ring were designed and synthesised. Structure‐activity relationships with the parent structure provided information that could direct further investigation on structure modification. Copyright © 2012 Society of Chemical Industry     

Nitrogen metabolism disorder in watermelon leaf caused by fusaric acid

The effect of fusaric acid (FA) on the activity of leaf nitrogen (N) metabolism enzymes in watermelon seedlings supplied with different N forms was studied. The results showed that FA inhibited nitrogen uptake and caused decreased leaf amide and protein but increased the content of ammonium and amino acids. When treated with FA the activities of enzymes in the pathway for the synthesis of amino acid in leaves (GS, GOGAT, and GDH) were decreased by 15–23%, 13–40%, and 71–86%, respectively. The activity of asparagine synthetase was decreased by 34–57%. The proteinase activity was initially increased by 37–125% at 12 h after treatment of FA but then subsequently decreased. The activity of glutamate-pyruvate aminotransferase was increased by 280–400%, though the activity of glutamate-oxaloacetate aminotransferase was decreased by 30–63%. It was suggested that FA inhibited the uptake of ammonium in seedlings and suppressed the activities of amino acid and amide synthases, while stimulating proteinase activity.A new pathogenic mechanism of watermelon infection by Fusarium spp. was found as FA caused the complete disorder and collapse of the host plant's nitrogen metabolism. This work provides a new insight into the progression of watermelon wilting caused by Fusarium oxysporum f.sp. niveum.     

Pyridazinones as bioregulators in crop protection

Substituted pyridazinones induced specific decreases in the linolenic acid content accompanied by increases in the linoleic acid content of plant membranes. The ratio of linoleic acid to linolenic acid was used to establish structure-activity correlations for a series of about 50 different substituted pyridazinones. The most active compound found was 4-chloro-5-dimethylamino-2-phenylpyridazin-3-one. X-ray structural analysis of this compound yielded three types of crystals differing in their molecular parameters. Application of computerised cluster analysis confirmed the specific biological activity of selected groups of compounds. Electron-density calculations yielded substituents with specific activity on the linoleic acid/linolenic acid ratio. Correlation of this ratio, produced by different substituted pyridazinones, can be used to search for potentially more active compounds. Treatment of plants, moulds and insects with pyridazinones led to interesting results of importance to agriculture, and confirmed the bioregulator activity of some of these compounds.     

Physiological activity spectra of existing graminicides and the new herbicide 2-(2-benzothiazolyl-oxy)-N-methyl-N-phenylacetamide (mefenacet)

inhibitory activities of existing graminicides on root regeneration from monocotyledonous (oat) and dicotyledonous (soybean) plant cuttings in the light, in the dark and on algal growth were compared with the respective inhibitory activities of the new herbicide 2-(2-benzothiazo-lyl-oxy)-N-methyl-N-phenylacetamide (mefenacet). The mefenacet activity spectrum resembled that of the α-chloroacetamide herbicides. Herbicide groups of other structure-activity can be distinguished by their distinct activity spectrum. The mono-oxygenase inhibitors piperonyl but-oxide (PBO) and 1-aminobenzotriazole (ABT) were found to antagonize the inhibitory activities of herbicides from the thiolcarbamate, α-chloroacetamide, and oxyacetic acid amide structure groups in the oat rooting and leaf growth tests. The critical evaluation of the presently available information on graminicide and safener mode of action suggests the concept that lipid biosynthesis on the physiological level and mono-oxygenase type enzymes on the biochemical level may hold the target sites for many of the graminicides and safeners discussed.     

三种化学物质诱导观赏百合青霉病抗性的研究

采用水杨酸、纳米硅、氯化铵等3种化学物质对观赏百合青霉病的抑菌活性和诱抗效果进行了测定。结果表明,3种化学物质对观赏百合青霉病菌抑菌率较低,最高仅为5.6%。3种化学物质处理百合鳞茎后,表现出较高诱导抗病性。在100、50和25μg/ml浓度下,水杨酸的诱导抗病效果最好,分别为79.09%、69.28%和61.96%。浓度为100μg/ml的水杨酸、纳米硅和氯化铵处理观赏百合鳞茎后,再进行挑战接种,1d后鳞茎组织内过氧化物酶、苯丙氨酸解氨酶、β-1,3-葡聚糖酶活性明显高于对照。浓度为100μg/ml的3种化学物质处理百合种球在2℃条件下贮存4个月后,青霉病的发病率和病情指数均低于对照;水杨酸、纳米硅和氯化铵处理的诱导防治效果分别为60.89%、55.56%和35.31%;处理种球种植后能够正常萌发,出苗率分别为91.67%、90.83%、90.83%。