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[PMID]: 26771387 [Au] Autor: Hsu HC; Chang WM; Wu JY; Huang CC; Lu FJ; Chuang YW; Chang PJ; Chen KH; Hong CZ; Yeh RH; Liu TZ; Chen CH [Ad] Endereço: Department of Physical Medicine and Rehabilitation, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan. [Ti] Título: Folate Deficiency Triggered Apoptosis of Synoviocytes: Role of Overproduction of Reactive Oxygen Species Generated via NADPH Oxidase/Mitochondrial Complex II and Calcium Perturbation. [So] Source: PLoS One;11(1):e0146440, 2016. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA. [Mh] Termos MeSH primário: Cálcio/metabolismo Complexo II de Transporte de Elétrons/metabolismo Deficiência de Ácido Fólico/metabolismo NADPH Oxidases/metabolismo Espécies Reativas de Oxigênio/metabolismo [Mh] Termos MeSH secundário: Animais Apoptose/efeitos dos fármacos Carboxina/farmacologia Linhagem Celular Complexo II de Transporte de Elétrons/antagonistas & inibidores Ácido Fólico/metabolismo Células HeLa Seres Humanos NADPH Oxidases/antagonistas & inibidores Oxirredução/efeitos dos fármacos Estresse Oxidativo/fisiologia Coelhos Rotenona/farmacologia Sulfonas/farmacologia Tenoiltrifluoracetona/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Reactive Oxygen Species); 0 (Sulfones); 03L9OT429T (Rotenone); 326-91-0 (Thenoyltrifluoroacetone); 34284-75-8 (4-(2-aminoethyl)benzenesulfonylfluoride); 5A8K850HDE (Carboxin); 935E97BOY8 (Folic Acid); EC 1.3.5.1 (Electron Transport Complex II); EC 1.6.3.- (NADPH Oxidases); SY7Q814VUP (Calcium) [Em] Mês de entrada: 1607 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160116 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0146440

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[PMID]: 26763396 [Au] Autor: Kimura M; Mizukami S; Watanabe Y; Hasegawa-Baba Y; Onda N; Yoshida T; Shibutani M [Ad] Endereço: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology. [Ti] Título: Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens. [So] Source: J Toxicol Sci;41(1):91-104, 2016 Feb. [Is] ISSN: 1880-3989 [Cp] País de publicação: Japan [La] Idioma: eng [Ab] Resumo: We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration. [Mh] Termos MeSH primário: Antraquinonas/administração & dosagem Antraquinonas/toxicidade Rim/citologia Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos Nitrofurantoína/administração & dosagem Nitrofurantoína/toxicidade Propano/análogos & derivados [Mh] Termos MeSH secundário: Animais Peso Corporal/efeitos dos fármacos Carboxina/administração & dosagem Carboxina/toxicidade Proliferação Celular/efeitos dos fármacos Cloridrinas/administração & dosagem Cloridrinas/toxicidade Histonas/metabolismo Rim/efeitos dos fármacos Masculino Tamanho do Órgão/efeitos dos fármacos Propano/administração & dosagem Propano/toxicidade Ratos Endogâmicos F344 Fatores de Tempo Triantereno/administração & dosagem Triantereno/toxicidade Ubiquitinas/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Anthraquinones); 0 (Chlorohydrins); 0 (Histones); 0 (UBD protein, human); 0 (Ubiquitins); 3MJ7QCK0Z0 (1,2,3-trichloropropane); 5A8K850HDE (Carboxin); 927AH8112L (Nitrofurantoin); RF75O3IKOZ (1-amino-2,4-dibromoanthraquinone); T75W9911L6 (Propane); WS821Z52LQ (Triamterene); ZL0FUS96WW (1-chloro-2-propanol) [Em] Mês de entrada: 1609 [Cu] Atualização por classe: 160114 [Lr] Data última revisão: 160114 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160115 [St] Status: MEDLINE [do] DOI: 10.2131/jts.41.91

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[PMID]: 26038251 [Au] Autor: Yu J; Zhang Y; Cui H; Hu P; Yu X; Ye Z [Ad] Endereço: Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, China. [Ti] Título: An efficient genetic manipulation protocol for Ustilago esculenta. [So] Source: FEMS Microbiol Lett;362(12):fnv087, 2015 Jun. [Is] ISSN: 1574-6968 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Ustilago esculenta grows within the flowering stem of the aquatic grass Zizania latifolia, resembling a fungal endophyte. The fungus colonizes Z. latifolia and induces swelling which results in the formation of galls near the base of the plant. Due to their unique flavor and textures these galls are considered as a delicacy in southern China. Efficient genetic manipulation is required to determine the relationship between U. esculenta and Z. latifolia. In this study, we report a protoplast-based transformation system for this unique fungal species. We have explored various factors (enzyme digesting conditions, osmotic pressure stabilizers, vectors and selection agents) that might impact protoplast yield and high frequencies of transformation. A haploid strain (UeT55) of U. esculenta was found to produce higher yields of protoplasts when treating with 15 mg mL(-1) lywallzyme in a sucrose-containing solution at 30°C for 3 h. The transformation frequencies were higher when fungal strain was transformed with a linear plasmid harboring hygromycin or carboxin resistance gene and regenerated on a sucrose-containing medium. A UeICL gene (coding isocitrate lyase) was disrupted and an EGFP (coding enhanced green fluorescent protein) gene was overexpressed successfully in the UeT55 strain using the developed conditions. The genetic manipulation system reported in this study will open up new opportunities for forward and reverse genetics in U. esculenta. [Mh] Termos MeSH primário: Técnicas Genéticas Protoplastos/fisiologia Transformação Genética Ustilago/genética [Mh] Termos MeSH secundário: Carboxina/farmacologia Parede Celular/metabolismo Cinamatos/farmacologia Enzimas/metabolismo Haploidia Higromicina B/análogos & derivados Higromicina B/farmacologia Isocitrato Liase/genética Plasmídeos/genética Ustilago/efeitos dos fármacos Ustilago/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cinnamates); 0 (Enzymes); 3XQ2233B0B (Hygromycin B); 3YJY415DDI (hygromycin A); 5A8K850HDE (Carboxin); EC 4.1.3.1 (Isocitrate Lyase) [Em] Mês de entrada: 1512 [Cu] Atualização por classe: 161125 [Lr] Data última revisão: 161125 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150604 [St] Status: MEDLINE

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[PMID]: 25595298 [Au] Autor: Asad-Uz-Zaman M; Bhuiyan MR; Khan MA; Alam Bhuiyan MK; Latif MA [Ad] Endereço: Rice Farming systems Division, Bangladesh Rice Research Institute, Gazipur 1701, Bangladesh. [Ti] Título: Integrated options for the management of black root rot of strawberry caused by Rhizoctonia solani Kuhn. [So] Source: C R Biol;338(2):112-20, 2015 Feb. [Is] ISSN: 1768-3238 [Cp] País de publicação: France [La] Idioma: eng [Ab] Resumo: An investigation was made to manage strawberry black root rot caused by Rhizoctonia solani (R. solani) through the integration of Trichoderma harzianum (T. harzianum) isolate STA7, mustard oil cake and Provax 200. A series of preliminary experiments were conducted to select a virulent isolate of R. solani, an effective isolate of T. harzianum, a suitable organic amendment, and a suitable fungicide before setting the experiment for integration. The pathogenicity of the selected four isolates of R. solani was evaluated against strawberry and isolate SR1 was selected as the test pathogen due to its highest virulent (95.47% mortality) characteristics. Among the 20 isolates of T. harzianum, isolate STA7 showed maximum inhibition (71.97%) against the test pathogen (R. solani). Among the fungicides, Provax-200 was found to be more effective at lowest concentration (100 ppm) and highly compatible with Trichoderma isolates STA7. In the case of organic amendments, maximum inhibition (59.66%) of R. solani was obtained through mustard oil cake at the highest concentration (3%), which was significantly superior to other amendments. Minimum percentages of diseased roots were obtained with pathogen (R. solani)+Trichoderma+mustard oil cake+Provax-200 treatment, while the highest was observed with healthy seedlings with a pathogen-inoculated soil. In the case of leaf and fruit rot diseases, significantly lowest infected leaves as well as fruit rot were observed with a pathogen+Trichoderma+mustard oil cake+Provax-200 treatment in comparison with the control. A similar trend of high effectiveness was observed by the integration of Trichoderma, fungicide and organic amendments in controlling root rot and fruit diseases of strawberry. Single application of Trichoderma isolate STA7, Provax 200 or mustard oil cake did not show satisfactory performance in terms of disease-free plants, but when they were applied in combination, the number of healthy plants increased significantly. The result of the current study suggests the superiority of our integrated approach to control the sclerotia forming pathogen R. solani compared to the individual treatment either by an antagonist or by a fungicide or by mustard oil cake. [Mh] Termos MeSH primário: Basidiomycota/efeitos dos fármacos Fragaria/microbiologia Fungicidas Industriais/farmacologia Doenças das Plantas/prevenção & controle Óleos Vegetais/farmacologia Rhizoctonia/efeitos dos fármacos Trichoderma/fisiologia [Mh] Termos MeSH secundário: Alanina/análogos & derivados Alanina/farmacologia Basidiomycota/crescimento & desenvolvimento Basidiomycota/isolamento & purificação Basidiomycota/patogenicidade Benzimidazóis/farmacologia Carbamatos/farmacologia Carboxina/farmacologia Avaliação Pré-Clínica de Medicamentos Sinergismo Farmacológico Frutas/microbiologia Mostardeira Controle Biológico de Vetores Doenças das Plantas/microbiologia Folhas de Planta/microbiologia Raízes de Plantas/microbiologia Rhizoctonia/crescimento & desenvolvimento Rhizoctonia/isolamento & purificação Rhizoctonia/patogenicidade Microbiologia do Solo Virulência [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Benzimidazoles); 0 (Carbamates); 0 (Fungicides, Industrial); 0 (Plant Oils); 16K4M187IF (metalaxyl); 5A8K850HDE (Carboxin); H75J14AA89 (carbendazim); OF5P57N2ZX (Alanine); TYY1MA9BSY (mustard oil) [Em] Mês de entrada: 1510 [Cu] Atualização por classe: 161125 [Lr] Data última revisão: 161125 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150118 [St] Status: MEDLINE

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[PMID]: 25476396 [Au] Autor: Mbaye OM; Maroto A; Gaye-Seye MD; Stephan L; Deschamps L; Aaron JJ; Giamarchi P [Ad] Endereço: Laboratoire de Photochimie et d׳Analyse, Faculté des Sciences et Techniques, Université C.A. Diop, Dakar, Sénégal. [Ti] Título: A new direct laser photo-induced fluorescence method coupled on-line with liquid chromatographic separation for the simultaneous determination of anilides pesticides. [So] Source: Talanta;132:909-14, 2015 Jan. [Is] ISSN: 1873-3573 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: A new direct laser photo-induced fluorescence high performance liquid chromatography (DL-PIF-HPLC) method is developed for the simultaneous determination of three anilide pesticides, namely carboxin, monalide and propanil. DL-PIF-HPLC uses a tunable Nd:YAG-OPO laser to obtain fluorescent photoproduct(s) and to simultaneously analyze their fluorescence in a short acquisition time with an intensified CCD camera, which improves the selectivity (by choosing the suitable excitation wavelength), increases the sensitivity (due to the high energy of the laser beam) and reduces the time of analysis, relative to the classical PIF methods. However, one of the main drawbacks of PIF methods is the presence of interferences with other compounds, such as other pesticides from the same group yielding similar fluorescent photoproducts, which reduces their selectivity. The analytical interest of DL-PIF-HPLC to avoid these interferences is demonstrated. The DL-PIF spectra, chromatographic conditions and analytical performances of DL-PIF-HPLC are presented for the simultaneous determination of three anilide pesticides. The calibration curves are linear over one order of magnitude and the limits of detection are in the ng mL(-1) range. The new DL-PIF-HPLC system has the advantage to combine the performances of both techniques, DL-PIF and liquid chromatography, and to improve the analysis selectivity. [Mh] Termos MeSH primário: Carboxina/análise Cromatografia Líquida de Alta Pressão/métodos Praguicidas/análise Propanil/análise Espectrometria de Fluorescência/métodos [Mh] Termos MeSH secundário: Calibragem Cromatografia Líquida de Alta Pressão/instrumentação Lasers Luz Limite de Detecção Metanol Soluções Solventes Espectrometria de Fluorescência/instrumentação Água [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Pesticides); 0 (Solutions); 0 (Solvents); 059QF0KO0R (Water); 5A8K850HDE (Carboxin); 709-98-8 (Propanil); Y4S76JWI15 (Methanol) [Em] Mês de entrada: 1508 [Cu] Atualização por classe: 141205 [Lr] Data última revisão: 141205 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141206 [St] Status: MEDLINE

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[PMID]: 25911838 [Au] Autor: Singh RB; Singh HK; Parmar A [Ti] Título: Yield loss assessment due to Alternaria blight and its management in linseed. [So] Source: Pak J Biol Sci;17(4):511-6, 2014 Apr. [Is] ISSN: 1028-8880 [Cp] País de publicação: Pakistan [La] Idioma: eng [Ab] Resumo: Field experiments were conducted during 2010-11 and 2011-12 to assess the yield losses due to Alternaria blight disease caused by Alternaria lini and A. linicola in recently released cultivars and their management with the integration of Trichoderma viride, fungicides and plant extract. Disease severity on leaves varied from 41.07% (Parvati) to 65.01% (Chambal) while bud damage per cent ranged between 23.56% (Shekhar) to 46.12% (T-397), respectively in different cultivars. Maximum yield loss of 58.44% was recorded in cultivar Neelum followed by Parvati (55.56%), Meera (55.56%) and Chambal (51.72%), respectively while minimum loss was recorded in Kiran (19.99%) and Jeevan (22.22%). Minimum mean disease severity (19.47%) with maximum disease control (69.74%) was recorded with the treatment: seed treatment (ST) with vitavax power (2 g kg(-1) seed) + 2 foliar sprays (FS) of Saaf (a mixture of carbendazim+mancozeb) 0.2% followed by ST with Trichoderma viride (4g kg(-1) seed) + 2 FS of Saaf (0.2%). Minimum bud damage (13.75%) with maximum control (60.94%) was recorded with treatment of ST with vitavax power+2 FS of propiconazole (0.2%). Maximum mean seed yield (1440 kg ha(-1)) with maximum net return (Rs. 15352/ha) and benefit cost ratio (1:11.04) was obtained with treatment ST with vitavax power + 2 FS of Neem leaf extract followed by treatment ST with vitavax power+2 FS of Saaf (1378 kg ha(-1)). [Mh] Termos MeSH primário: Alternaria/efeitos dos fármacos Alternariose/prevenção & controle Azadirachta Linho/microbiologia Fungicidas Industriais/farmacologia Controle Biológico de Vetores Controle de Pragas/métodos Doenças das Plantas/prevenção & controle Trichoderma/fisiologia [Mh] Termos MeSH secundário: Aerossóis Alternaria/patogenicidade Alternariose/microbiologia Azadirachta/química Benzimidazóis/farmacologia Carbamatos/farmacologia Carboxina/farmacologia Linho/crescimento & desenvolvimento Maneb/farmacologia Doenças das Plantas/microbiologia Extratos Vegetais/isolamento & purificação Extratos Vegetais/farmacologia Folhas de Planta/crescimento & desenvolvimento Folhas de Planta/microbiologia Pós Triazóis/farmacologia Zineb/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Aerosols); 0 (Benzimidazoles); 0 (Carbamates); 0 (Fungicides, Industrial); 0 (Plant Extracts); 0 (Powders); 0 (Triazoles); 12427-38-2 (Maneb); 142KW8TBSR (propiconazole); 5A8K850HDE (Carboxin); H75J14AA89 (carbendazim); R0HY55EB9E (mancozeb); X1FSB1OZPT (Zineb) [Em] Mês de entrada: 1505 [Cu] Atualização por classe: 151119 [Lr] Data última revisão: 151119 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150428 [St] Status: MEDLINE

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[PMID]: 24119086 [Au] Autor: Lalève A; Gamet S; Walker AS; Debieu D; Toquin V; Fillinger S [Ad] Endereço: INRA, UR 1290 BIOGER-CPP, Avenue Lucien Brétignières, F-78850, Thiverval-Grignon, France. [Ti] Título: Site-directed mutagenesis of the P225, N230 and H272 residues of succinate dehydrogenase subunit B from Botrytis cinerea highlights different roles in enzyme activity and inhibitor binding. [So] Source: Environ Microbiol;16(7):2253-66, 2014 Jul. [Is] ISSN: 1462-2920 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Carboxamide fungicides target succinate dehydrogenase (SDH). Recent field monitoring studies have identified Botrytis cinerea isolates resistant to one or several SDH inhibitors (SDHIs) with amino acid substitutions in the SDH B subunit. We confirmed, by site-directed mutagenesis of the sdhB gene, that each of the mutations identified in field strains conferred resistance to boscalid in B.cinerea, and in some cases cross-resistance to other SDHIs (fluopyram, carboxin). Enzyme inhibition studies showed that the studied modifications (SdhB_P225T/L/F, N230I, H272Y/R/L) affected the inhibition of SDH activity by SDHIs, directly contributing to resistance. Our results confirm the importance of H272, P225 and N230 for carboxamide binding. Modifications of P225 and N230 conferred resistance to the four carboxamides tested (boscalid, fluopyram, carboxin, bixafen). Modifications of H272 had differential effects on the susceptibility of SDH to SDHIs. SdhB(H272L) , affected susceptibility to all SDHIs, SdhB(H272R) conferred resistance to all SDHIs tested except fluopyram, and SdhB(H272Y) conferred fluopyram hypersensitivity. Affinity-binding studies with radiolabelled fluopyram revealed strong correlations among the affinity of SDHIs for SDH, SDH inhibition and in vivo growth inhibition in the wild type. The sdhB(H272Y) mutation did not affect SDH and respiration activities, whereas all the other mutations affected respiration by decreasing SDH activity. [Mh] Termos MeSH primário: Botrytis/genética Proteínas Fúngicas/genética Subunidades Proteicas/genética Succinato Desidrogenase/genética [Mh] Termos MeSH secundário: Substituição de Aminoácidos Benzamidas Compostos de Bifenilo Botrytis/efeitos dos fármacos Botrytis/enzimologia Carboxina Farmacorresistência Fúngica/genética Inibidores Enzimáticos Proteínas Fúngicas/química Proteínas Fúngicas/metabolismo Fungicidas Industriais Mutagênese Sítio-Dirigida Niacinamida/análogos & derivados Ligação Proteica Subunidades Proteicas/química Subunidades Proteicas/metabolismo Piridinas Relação Estrutura-Atividade Succinato Desidrogenase/química Succinato Desidrogenase/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Benzamides); 0 (Biphenyl Compounds); 0 (Enzyme Inhibitors); 0 (Fungal Proteins); 0 (Fungicides, Industrial); 0 (Protein Subunits); 0 (Pyridines); 25X51I8RD4 (Niacinamide); 32MS8ZRD1V (2-chloro-N-(4-chlorobiphenyl-2-yl)nicotinamide); 5A8K850HDE (Carboxin); EC 1.3.99.1 (Succinate Dehydrogenase); F0VT7K5302 (N-(2-(3-chloro-5-(trifluoromethyl)-2-pyridyl)ethyl)-alpha,alpha,alpha-trifluoro-o-toluamide) [Em] Mês de entrada: 1410 [Cu] Atualização por classe: 140702 [Lr] Data última revisão: 140702 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 131015 [St] Status: MEDLINE [do] DOI: 10.1111/1462-2920.12282

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[PMID]: 22536383 [Au] Autor: Scalliet G; Bowler J; Luksch T; Kirchhofer-Allan L; Steinhauer D; Ward K; Niklaus M; Verras A; Csukai M; Daina A; Fonné-Pfister R [Ad] Endereço: Syngenta Crop Protection Münchwilen AG, Stein, Switzerland. gabriel.scalliet@syngenta.com [Ti] Título: Mutagenesis and functional studies with succinate dehydrogenase inhibitors in the wheat pathogen Mycosphaerella graminicola. [So] Source: PLoS One;7(4):e35429, 2012. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A range of novel carboxamide fungicides, inhibitors of the succinate dehydrogenase enzyme (SDH, EC 1.3.5.1) is currently being introduced to the crop protection market. The aim of this study was to explore the impact of structurally distinct carboxamides on target site resistance development and to assess possible impact on fitness. We used a UV mutagenesis approach in Mycosphaerella graminicola, a key pathogen of wheat to compare the nature, frequencies and impact of target mutations towards five subclasses of carboxamides. From this screen we identified 27 amino acid substitutions occurring at 18 different positions on the 3 subunits constituting the ubiquinone binding (Qp) site of the enzyme. The nature of substitutions and cross resistance profiles indicated significant differences in the binding interaction to the enzyme across the different inhibitors. Pharmacophore elucidation followed by docking studies in a tridimensional SDH model allowed us to propose rational hypotheses explaining some of the differential behaviors for the first time. Interestingly all the characterized substitutions had a negative impact on enzyme efficiency, however very low levels of enzyme activity appeared to be sufficient for cell survival. In order to explore the impact of mutations on pathogen fitness in vivo and in planta, homologous recombinants were generated for a selection of mutation types. In vivo, in contrast to previous studies performed in yeast and other organisms, SDH mutations did not result in a major increase of reactive oxygen species levels and did not display any significant fitness penalty. However, a number of Qp site mutations affecting enzyme efficiency were shown to have a biological impact in planta.Using the combined approaches described here, we have significantly improved our understanding of possible resistance mechanisms to carboxamides and performed preliminary fitness penalty assessment in an economically important plant pathogen years ahead of possible resistance development in the field. [Mh] Termos MeSH primário: Ascomicetos/enzimologia Proteínas Fúngicas/genética Mutagênese Doenças das Plantas/microbiologia Succinato Desidrogenase/genética Triticum/microbiologia [Mh] Termos MeSH secundário: Sequência de Aminoácidos Ascomicetos/efeitos dos fármacos Ascomicetos/genética Ascomicetos/crescimento & desenvolvimento Benzamidas/farmacologia Sítios de Ligação Compostos de Bifenilo/farmacologia Carboxina/farmacologia Simulação por Computador Sequência Conservada Farmacorresistência Fúngica/genética Proteínas Fúngicas/antagonistas & inibidores Fungicidas Industriais/farmacologia Concentração Inibidora 50 Modelos Moleculares Dados de Sequência Molecular Niacinamida/análogos & derivados Niacinamida/farmacologia Norbornanos/farmacologia Estresse Oxidativo Ligação Proteica Pirazóis/farmacologia Piridinas/farmacologia Succinato Desidrogenase/antagonistas & inibidores [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (3-(difluoromethyl)-1-methyl-N-(1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl)pyrazole-4-carboxamide); 0 (Benzamides); 0 (Biphenyl Compounds); 0 (Fungal Proteins); 0 (Fungicides, Industrial); 0 (Norbornanes); 0 (Pyrazoles); 0 (Pyridines); 25X51I8RD4 (Niacinamide); 32MS8ZRD1V (2-chloro-N-(4-chlorobiphenyl-2-yl)nicotinamide); 5A8K850HDE (Carboxin); EC 1.3.99.1 (Succinate Dehydrogenase); F0VT7K5302 (N-(2-(3-chloro-5-(trifluoromethyl)-2-pyridyl)ethyl)-alpha,alpha,alpha-trifluoro-o-toluamide) [Em] Mês de entrada: 1208 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 120427 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0035429

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MEDLINE

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[PMID]: 21780142 [Au] Autor: Kano S; Akagi K; Kanematsu S; Morinaga T [Ad] Endereço: Department of Life System Science, Graduate School of Comprehensive Scientific Research, Prefectural University of Hiroshima, Shobara, Hiroshima, Japan. [Ti] Título: Cloning and characterization of the gene for the iron-sulfur subunit of succinate dehydrogenase from the violet root rot fungus, Helicobasidium mompa. [So] Source: J Basic Microbiol;52(2):132-40, 2012 Apr. [Is] ISSN: 1521-4028 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: The sdhB gene, encoding the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (Sdh, EC 1.3.99.1), has been cloned from the violet root rot fungus, Helicobasidium mompa, and characterized. The promoter region contains a CCAAT box, TATA-like box, and CT-rich region. The gene is interrupted by eight introns and is predicted to encode a polypeptide of 291 amino acid residues. The putative amino acid sequence of the encoded product of sdhB gene from H. mompa shows high homology to the other known sdhB genes and is 79% identical to the Ip subunit of SdhB of Uromyces fabae. Three cysteine-rich clusters associated with the iron-sulfur centers involved in electron transport were particularly well conserved. One of these clusters contains a critical histidine residue implicated in carboxin sensitivity in the basidiomycetes. Only one copy of the gene was present in the genome of H. mompa, and reverse transcription (RT)-PCR analysis of mRNA expression showed that the sdhB gene was transcribed in potato dextrose broth. [Mh] Termos MeSH primário: Basidiomycota/genética Proteínas Fúngicas/metabolismo Proteínas com Ferro-Enxofre/metabolismo Succinato Desidrogenase/metabolismo [Mh] Termos MeSH secundário: Sequência de Aminoácidos Sequência de Bases Basidiomycota/enzimologia Carboxina/farmacologia Clonagem Molecular DNA Fúngico/genética Proteínas Fúngicas/genética Íntrons Proteínas com Ferro-Enxofre/genética Dados de Sequência Molecular Filogenia Regiões Promotoras Genéticas Reação em Cadeia da Polimerase Via Transcriptase Reversa Análise de Sequência de DNA Succinato Desidrogenase/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (DNA, Fungal); 0 (Fungal Proteins); 0 (Iron-Sulfur Proteins); 5A8K850HDE (Carboxin); EC 1.3.99.1 (Succinate Dehydrogenase) [Em] Mês de entrada: 1207 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 110723 [St] Status: MEDLINE [do] DOI: 10.1002/jobm.201100014

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MEDLINE

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[PMID]: 21721531 [Au] Autor: Obermayer D; Glasnov TN; Kappe CO [Ad] Endereço: Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria. [Ti] Título: Microwave-assisted and continuous flow multistep synthesis of 4-(pyrazol-1-yl)carboxanilides. [So] Source: J Org Chem;76(16):6657-69, 2011 Aug 19. [Is] ISSN: 1520-6904 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A series of 4-(pyrazol-1-yl)carboxanilides active as inhibitors of canonical transient receptor potential channels were synthesized in an efficient three-step protocol using controlled microwave heating. The general synthetic strategy involves condensation of 4-nitrophenylhydrazine with appropriate 1,3-dicarbonyl building blocks, followed by reduction of the nitro group to the amine, which is then amidated with carboxylic acids. Compared to the conventional protocol a dramatic reduction in overall processing time from ~2 days to a few minutes was achieved, accompanied by significantly improved product yields. In addition, the first two steps in the synthetic pathway were also performed under continuous flow conditions providing similar isolated product yields. As an alternative to the three-step protocol, a novel two-step route to the desired 4-(pyrazol-1-yl)carboxanilides was devised involving condensation of 4-bromophenylhydrazine with appropriate 1,3-dicarbonyl building blocks, followed by Pd-catalyzed Buchwald-Hartwig amidation with carboxylic acid amides. [Mh] Termos MeSH primário: Amidas/química Carboxina/análogos & derivados Carboxina/síntese química Pirazóis/síntese química [Mh] Termos MeSH secundário: Carboxina/química Catálise Calefação Micro-Ondas Estrutura Molecular Pirazóis/química [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Amides); 0 (Pyrazoles); 3QD5KJZ7ZJ (pyrazole); 5A8K850HDE (Carboxin) [Em] Mês de entrada: 1112 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 110705 [St] Status: MEDLINE [do] DOI: 10.1021/jo2009824

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