Multicomponent reactions in crop protection chemistry.

An overview is given of the significance of multicomponent reactions in the synthesis of agrochemicals. The most important applications of multicomponent condensations, such as the Biginelli reaction, Bucherer-Bergs reaction, Hantzsch dihydropyridine synthesis, Kabachnik-Fields reaction, Mannich reaction, Passerini reaction, Petasis reaction, Strecker reaction, Ugi reaction and Willgerodt-Kindler reaction, to the synthesis of herbicidally, fungicidally and insecticidally active compounds are presented. Also the mode of action and biological activity of these multicomponent reaction products are reported.

Antibacterial and antifungal activities of different polar extracts from Anoectochilus roxburghii.

This study evaluates the antibacterial and antifungal activities of petroleum ether, acetic ether, n-butanol and aqueous extracts from Anoectochilus roxburghii. The in vitro antibacterial and antifungal effects against three bacterial strains (Escherichia coli, Bacillus subtilis, Bacillus thuringiensis) and three fungal species (Exserohilum turcicum (Pass.) Leonard et Suggs, Botrytis cinerea Pers., Fusahum graminearum Sehw.) were assayed by the dilution and disc-diffusion methods. All of the polar extracts expressed dose-dependent antimicrobial activity against all tested microorganisms. The most active extract was aqueous extract, with a minimum inhibitory concentration below 0.625mg/ml in both bacteria and fungi. The results suggest that new chemical classes of natural antimicrobial substances (such as A. roxiburghii extracts) can be selectively exploited for the chemotherapy and control of infectious diseases.

Design, synthesis and biological evaluation of novel nicotinamide derivatives bearing a substituted pyrazole moiety as potential SDH inhibitors.

BACKGROUND: Succinate dehydrogenase (SDH) plays an important role in the Krebs cycle, which is considered as an attractive target for development of succinate dehydrogenase inhibitors (SDHIs) based on antifungal agents. Thus, in order to discover novel molecules with high antifungal activities, SDH as the target for a series of novel nicotinamide derivatives bearing substituted pyrazole moieties were designed and synthesised via a one-pot reaction. RESULTS: The biological assay data showed that compound 3 l displayed the most potent antifungal activity with EC50 values of 33.5 and 21.4 µm against Helminthosporium maydis and Rhizoctonia cerealis, respectively. Moreover, 3 l exhibited the best inhibitory ability against SDH enzymes. The results of docking simulation showed that 3 l was deeply embedded into the SDH binding pocket, and the binding model was stabilised by a cation-π interaction with Arg 43, Tyr 58 and an H-bond with Trp 173. CONCLUSION: The study suggests that the pyrazole nicotinamide derivative 3 l may serve as a potential SDHI that can be used as a novel antifungal agent, and provides valuable clues for the further design and optimisation of SDH inhibitors. © 2016 Society of Chemical Industry.

[Cultural Properties and Taxonomic Position of Helminthosporium-Like Fungal Isolates from the White Sea].

Morphological, cultural and physiological characteristics of 19 Helminthosporium-like hyphomycetes isolated from the White Sea were studied. Taxonomic status of the isolates was verified using molecular genetics techniques. One of the isolates was identified as Alternatia sp., while the rest of marine isolates belonged to the species Paradendriphiella salina (G.K. Sutherl.) Woudenb. & Crous. The specific features of the isolates studied were characterized as adaptive. Optimum salinity for their growth was 1-2% NaCl, which is lower than the value for the known open ocean isolates. This is probably due to relatively low salinity of White Sea (22-24 per thousand) as compared with the ocean water (35 per thousand). While the temperature optimum for growth was 22 per thousand, growth and sporulation occurred at 6 degrees C, which has not been reported for marine fungi isolated from warmer seawater. All isolates studied grew and sporulated efficiently on the medium supplied with the Fucus algae extract and in the sea water layer. Conidia of the isolates submerged in the sea water were propagated efficiently, unlike the soil-born fungi. Holoblastic conidiogenesis was demonstrated by light and scanning electron microscopy, confirming the separation of P. salina from the genus Scolecobasidium.

Design, synthesis and bioactivity of novel glycosylthiadiazole derivatives.

A series of novel glycosylthiadiazole derivatives, namely 2-phenylamino-5-glycosyl-1,3,4-thiadiazoles, were designed and synthesized by condensation between sugar aldehydes A/B and substituted thiosemicarbazide C followed by oxidative cyclization by treating with manganese dioxide. The original fungicidal activities results showed that some title compounds exhibited excellent fungicidal activities against Sclerotinia sclerotiorum (Lib.) de Bary and Pyricularia oryzae Cav, especially compounds F-5 and G-8 which displayed better fungicidal activities than the commercial fungicide chlorothalonil. At the same time, the preliminary studies based on the Elson-Morgan method indicated that many compounds exhibited some inhibitory activity toward glucosamine-6-phosphate synthase (GlmS). The structure-activity relationships (SAR) are discussed in terms of the effects of the substituents on both the benzene and the sugar ring.

A new cyclopeptide with antifungal activity from the co-culture broth of two marine mangrove fungi.

A new cyclic tetrapeptide, cyclo-(L-leucyl-trans-4-hydroxy-L-prolyl-D-leucyl-trans-4-hydroxy-L-proline) (1), was isolated from the co-culture broth of two mangrove fungi Phomopsis sp. K38 and Alternaria sp. E33. The structure of 1 was determined by analysis of spectroscopic data and Marfey's analytic method. Primary bioassay demonstrated that compound 1 exhibited moderate to high inhibitory activity against four crop-threatening fungi including Gaeumannomyces graminis, Rhizoctonia cerealis, Helminthosporium sativum and Fusarium graminearum as compared with triadimefon.

NORTHERN LEAF BLIGHT HELMINTHOSPORIUM TURCICUM ON MAIZE IN LATVIA.

In Latvia, climatic factors are influential in spreading of the Northern leaf blight of maize caused by Setosphaeria turcica (SETOTU, anamorph Exserohilum turcicum, Helminthosporium turcicum). The field experiments with the aim to investigate the effect of strobilurines to control of SETOTU in maize and the possibility to have a greening effect on yield and the silage quality parameters there were conducted in Latvian Plant Protection Research Centre in 2010. The effect of fungicides under natural and artificial infection with SETOTU on yield of maize was evaluated in 2012 and 2013. Trials designed with four replicates using randomized blocks, a plot size of 30 m2. Plots were inoculated at beginning of anthesis stage of maize by conidium of local population of H. turcicum propagated on PDA. Application of fungicides has been done in two times. Weather conditions were favourable for infestation of Northern leaf blight in maize. Disease severity was recorded according to the EPPO Guideline PP 1/272(1) on 10 plants from two central rows by 5 layers of leaves. Yield was recorded from two central separately harvested rows of each plot. The silage quality parameters in 2010 were analysed by Blgg BV Company, Netherlands. After the artificial inoculation an increase of the disease pressure in maize was observed. A good effect of the fungicides to control SETOTU was observed in all trials. No significant differences in efficacy were found between the treatments of Propulse (fluopyram 125 g L(-1), prothioconazole 125 g L(-1)), Opera (epoxiconazole 75, pyraclostrobin 199, 5 g L(-1) and Opera N (epoxiconazole 75, pyraclostrobin 102 g L(-1)). The effect of application time at the BBCH 55-59 was higher compared with application time at the BBCH 30-37. Two applications of Propulse compared with the single showed higher effect on SETOTU. The prolonged effect of Propulse on SETOTU was similar to Opera and Opera N. Greening effect was significant for all treatments compared with the untreated. In all treatments the increase of yield of fresh and dry mass was significant to the untreated. The positive influence of Opera N on the feed milk unit (VEM), protein (DVE, VOS, RP), digest OM (VCOS), starch, FAT content, NEL, energy metabolite (ME), nXP, UDP was recorded. The treatment of Opera N showed a tendency to decrease the silage quality parameters such as fatty acid vola (FOS), crude fiber (RF), crude ASH (RA), sugar content, acid det. fiber (ADF), acid det. lignin (ADL).

Purification and characterization of an antifungal peptide with potent antifungal activity but devoid of antiproliferative and HIV reverse transcriptase activities from Legumi secchi beans.

A monomeric 9.4-kDa peptide with antifungal activity was isolated from seeds of Phaseolus vulgaris cv Legumi secchi by using a protocol that involved affinity chromatography on Blue-Sepharose, ion exchange chromatography on Q-Sepharose, and gel filtration on Superdex 75. It was adsorbed on Blue-Sepharose and unadsorbed on Q-Sepharose. Its N-terminal sequence resembled those of other leguminous defensins. It impeded mycelial growth in the fungi Helminthosporium maydis, Rhizoctonia solani, Mycosphaerella arachidicola, and Fusarium oxysporum with an IC(50) value of 9.5, 3.5, 1, and 9.2 µM, respectively, but there was no effect on Valsa mali. SYTOX Green uptake by R. solani indicated that the antifungal peptide induced fungal membrane permeabilization. In contrast to the majority of previously reported defensins/defensin-like peptides, Legumi secchi antifungal peptide did not reduce the viability of MCF-7 breast cancer cells and HepG2 hepatoma cells or inhibit HIV-1 reverse transcriptase, indicating a dissociation between antifungal, antiproliferative and HIV-1 reverse transcriptase inhibitory activities.

[Screening of antifungi endophytic actinomyces strains from salvia przewalskii in Tibean Plateau].

Twenty-four endophytic actinomycetes strains were isolated from the Salvia przewalskii in Tibetan Plateau of China by tablet coating method. Fusarium moniliforme, Helminthosporium turcicum and Bipolaris maydis were selected as indicator fungi to test the antimicrobial activities of these endophytic actinomycetes by tablet confrontation method. The results showed that 21 strains can produce antimicrobial substances which accounts for 85.7% of the total separates number. Four strains of endogenous actinomyces have more obvious antifungi activity. According to results of morphology and culture properties and 16S rDNA sequences of endophytic actinomyces, it is concluded that all of the isolates were streptomycetes trains.

A regioselective synthesis of some new pyrazol-1'-ylpyrazolo[1,5-a]pyrimidines in aqueous medium and their evaluation as antimicrobial agents.

An efficient and environmental benign regioselective synthesis of some new pyrazol-1'-ylpyrazolo[1,5-a]pyrimidines (7b-h) has been accomplished via treatment of 3(5)-amino-5(3)-hydrazinopyrazole dihydrochloride (5) with several unsymmetrical 1,3-diketones (6b-h) using water as a solvent without any catalysts or additives. The structure of 7b-h was established on the basis of rigorous analysis of (1)H, (13)C NMR, IR spectral data and MS. Eight compounds (7a-h) were screened for their antibacterial activity against two gram-positive and two gram-negative bacteria and compounds (7a, b, d and e) for antifungal activity against four phytopathogenic fungi. Compounds 7c and 7e manifest rather broad antibacterial activity than standard antibiotics. One lead compound, 7a (10mg/ml and 200mg/ml) exhibited equipotent or more potent antifungal activity against all tested microorganisms than standard drug.

Effect of water activity on the production of volatile organic compounds by Muscodor albus and their effect on three pathogens in stored potato.

Muscodor albus (Xylariaceae, Ascomycetes) isolate CZ-620 produces antimicrobial volatile organic compounds (VOC), which appear to have potential for the control of various postharvest diseases. The effect of water activity (Aw) on the production of VOC by M. albus culture, and their inhibitory effects on the growth of three pathogens of potato tuber (Fusarium sambucinum, Helminthosporium solani, and Pectobacterium atrosepticum) and the development of diseases caused by the three pathogens (dry rot, silver scurf, and bacterial soft rot, respectively) were investigated. Rye grain culture of the fungus produced six alcohols, three aldehydes, five acids or esters, and two terpenoids. The most abundant VOC were: isobutyric acid; bulnesene, a sesquiterpene; an unidentified terpene; 2 and 3-methyl-1-butanol; and ethanol. However, the level of each of those VOC varied with Aw of the culture. Emission activity occurred mainly at Aw above 0.75 and high emission of most VOC occurred only at Aw above 0.90. The aldehydes (2-methyl-propanal and 3-methyl-butanal) were the only VOC produced in quantities below an Aw of 0.90. An Aw value of 0.96 favored maximum emission of acids, esters, and terpenoids. There was a higher production of alcohols and a decrease in aldehydes with increase in Aw. Isobutyric acid, which has been the main M. albus VOC monitored in previous studies as an indicator of antifungal activity, had a rather narrow optimum, peaking at Aw of 0.96 and declining sharply above 0.98. Results showed that substrate Aw affects the production dynamics of each group of VOC by the fungus, and suggest that VOC production can be prolonged by maintaining M. albus culture at a constant optimum Aw. The VOC was inhibitory to F. sambucinum, H. solani, and P. atrosepticum; and biofumigation with M. albus significantly reduced dry rot and soft rot development, and completely controlled silver scurf in inoculated tubers incubated at both 8°C and 22°C. The results show that Aw of grain culture affects the production of VOC by M. albus; and that the VOC inhibit the growth of the tested pathogens and the diseases caused by them in potato tubers.

Acaconin, a chitinase-like antifungal protein with cytotoxic and anti-HIV-1 reverse transcriptase activities from Acacia confusa seeds.

From the seeds of Acacia confusa, a chitinase-like antifungal protein designated as acaconin that demonstrated antifungal activity toward Rhizoctonia solani with an IC50 of 30±4 µM was isolated. Acaconin demonstrated an N-terminal sequence with pronounced similarity to chitinases and a molecular mass of 32 kDa. It was isolated by chromatography on Q-Sepharose, SP-Sepharose and Superdex 75 and was not bound by either ion exchanger. Acaconin was devoid of chitinase activity. The antifungal activity against Rhizoctonia solani was completely preserved from pH 4 to 10 and from 0°C to 70°C. Congo Red staining at the tips of R. solani hyphae indicated inhibition of fungal growth. However, there was no antifungal activity toward Mycosphaerella arachidicola, Fusarium oxysporum, Helminthosporium maydis, and Valsa mali. Acaconin inhibited proliferation of breast cancer MCF-7 cells with an IC50 of 128±9 µM but did not affect hepatoma HepG2 cells. Its IC50 value toward HIV-1 reverse transcriptase was 10±2.3 µM. The unique features of acaconin include relatively high stability when exposed to changes in ambient pH and temperature, specific antifungal and antitumor actions, potent HIV-reverse transcriptase inhibitory activity, and lack of binding by strongly cationic and anionic exchangers.

Antifungal activities of some indole derivatives.

Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide.

Synthesis and antifungal activities of some 2,6-bis-(un)substituted phenoxymethylpyridines.

Several 2,6-bis-(un)substituted phenoxymethylpyridines were synthesized and evaluated in vitro against Fusarium graminearum, Helminthosporium sorokinianum, Alternaria brassicae, Alternaria alternata, and Fusarium oxysporum f. sp. vasinfectum. Among all derivatives, compound 3a exhibited a broad-spectrum antifungal activity against the five phytopathogenic fungi.

Synthesis and antimicrobial activity of novel phosphorus heterocycles with exocyclic p-C link.

Several new class of phosphorus heterocyclic compounds containing exocyclic P-C link such as 6-(2'-chloroethyl)/(allyl)/(benzyl)-1,2,4,8,10,11-hexachloro-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxides (5-7), 2-(2"-chloroethyl)/(allyl)-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihdro-2H-1,3,2-benzoxazaphosphorin 2-oxides (9, 10), 2-(2"-chloroethyl-2,3-dihydro-3-(4'-bromophenyl)-1H-naphth[1,2-e][1,3,2]-oxazaphosphorin 2-oxide (12), 2-(2"-chloroethyl)/(allyl)-2,3-dihydro-5-benzoyl-1H-1,3,2-benzodiazaphosphole 2-oxides (14, 15), 4-phenyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phosphapentalene 2-oxide (17) and 4-benzyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phospha-pentalene 2-oxide (19) were synthesized by reacting equimolar quantities of corresponding diol (4)/diamines (13, 16, 18), 2-cyclohexylaminomethyl-4-t-butylphenol (8) and 1-(4'-bromoanilinomethyl)-2-naphthol (11), with respective phosponyl dichlorides (1-3) in dry toluene/toluene-tetrahydro-furan/pyridine in the presence of triethylamine at various temperatures. Their structures were established by IR, (1)H-, (13)C- and (31)P-NMR spectral data. The mass spectral data were given for compounds 9, 12 and 15. The title compounds were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli and antifungal activity on Aspergillus niger and Helminthosporium oryzae. Most of the compounds possess significant activity.

[Protein and peptide factors from Bacillus sp.739 inhibit the growth of phytopathogenic fungi]. / Belkovye i peptidnye factory Bacillus sp.739--ingibitory rosta fitopatogennykh gribov.

Thermolabile peptides inhibiting the growth of Helminthosporium sativum, a facultative phytopathogen, have been isolated from the low-molecular-weight fraction of extracellular metabolites of the strain Bacillus sp. 739. Paper chromatography of the fraction, followed by bioautography, revealed the presence of three components exhibiting antifungal activity. These components were separated by gel chromatography on Toyopearl HW-40. SDS-PAGE (the Laemmli procedure) demonstrated that only one component was a protein (MW, approximately 14 kDa). The other two substances were polypeptides with molecular weights less than 6 kDa each. The protein factor inhibited the growth of H. sativum with a minimum effective concentration of 0.1 to 0.2 mg/ml.

Synthesis and antimicrobial activities of some new 2-substituted benzoxazole/benzothiazole derivatives.

In the search for new antimicrobial compounds, several new sulfur bearing heterobicyclic moieties (4-11) have been synthesized by acylation and alkylation of acetamide, thioacetamide and semicarbazide derivatives. The structure of the products was deduced from elemental analyses as well as spectral data (IR, 1H NMR and MS). Significant antimicrobial activities were obtained for all new compounds especially against Fusarium oxysporum.

A PCR-based method to characterise and identify benzimidazole resistance in Helminthosporium solani.

Control of Helminthosporium solani, the cause of silver scurf in potato tubers, has been impaired by selection of benzimidazole-resistant strains as a result of repeated use of the fungicide thiabendazole. Identification of thiabendazole-resistant strains of H. solani by conventional techniques takes several weeks. Primers designed from conserved regions of the fungal beta-tubulin gene were used to PCR amplify and sequence a portion of the gene. A point mutation was detected at codon 198 in thiabendazole-resistant isolates causing a change in the amino acid sequence from glutamic acid to alanine or glutamine. Species-specific PCR primers designed to amplify this region were used in conjunction with a restriction endonuclease to cause cleavage in sensitive isolates only and thus provide a rapid diagnostic test to differentiate field isolates.

Fungicidal action and structure correlation of monosubstituted phenyl isothiocyanates.

The fungicidal activity of 10 monosubstituted phenyl isothiocyanates was observed with four plant pathogens. The ortho- and meta-substituted derivatives possessed a fair activity while the para-substituted ones proved to be highly fungicidal when compared to the control Agrosan GN.