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Xianwen Yang - One of the best experts on this subject based on the ideXlab platform.
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botryotins a h tetracyclic diterpenoids representing three carbon skeletons from a deep sea derived Botryotinia fuckeliana
Organic Letters, 2020Co-Authors: Siwen Niu, Guizhen Peng, Chunlan Xie, Jinmei Xia, Qingmei Liu, Guangming Liu, Xianwen YangAbstract:Eight unprecedent diterpenoids, botryotins A–H (1–8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2–6), and 6/6/6/5 (7 and 8) t...
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a new pimarane diterpenoid from the Botryotinia fuckeliana fungus isolated from deep sea water
Chemistry & Biodiversity, 2019Co-Authors: Siwen Niu, Guizhen Peng, Chunlan Xie, Jinmei Xia, Xianwen YangAbstract:A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20 μm).
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aphidicolin chemistry of the deep sea derived fungus Botryotinia fuckeliana mccc 3a00494
Journal of Natural Products, 2019Co-Authors: Zengpeng Li, Zhiwei Yi, Guizhen Peng, Longhe Yang, Zongze Shao, Xianwen YangAbstract:Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1–A71, 1–71) and eight known (72–79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (−5572 m). The structures of 1–71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher’s method, and the ECD exciton chirality method. Compounds 54–57 and 58–64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65–71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 μM) and HL-60 (IC50 = 6.1 μM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to...
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aphidicolin chemistry of the deep sea derived fungus Botryotinia fuckeliana mccc 3a00494
Journal of Natural Products, 2019Co-Authors: Siwen Niu, Guizhen Peng, Longhe Yang, Zongze Shao, Chunlan Xie, Jinmei Xia, Zhuhua Luo, Xianwen YangAbstract:Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 μM) and HL-60 (IC50 = 6.1 μM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.
Francesco Faretra - One of the best experts on this subject based on the ideXlab platform.
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effects of polysaccharides from Botryotinia fuckeliana botrytis cinerea on in vitro culture of table and wine grapes vitis vinifera
Vitis: Journal of Grapevine Research, 2015Co-Authors: G Fanizza, Stefania Pollastro, V Bisignano, Monica Marilena Miazzi, Francesco FaretraAbstract:Shoots of several table and wine grape cultivars were cultured in vitro on a medium supplemented with polysaccharides obtained from a culture filtrate of Botryotinia fuckeliana through differential ethanolic precipitations. The general effects of polysaccharides resulted in leaf yellowness and in a reduction of fresh and dry weight. Differential response of assayed cultivars to polysaccharides seemed to be not related to their bunch susceptibility to grey mould under field conditions.
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occurrence of fungicide resistance in populations of Botryotinia fuckeliana botrytis cinerea on table grape and strawberry in southern italy
Pest Management Science, 2014Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, D Gerin, Stefania Pollastro, Caterina Rotolo, Francesco FaretraAbstract:BACKGROUND Botryotinia fuckeliana (Botrytis cinerea) is a pathogen with a high risk of development of resistance to fungicides. Fungicide resistance was monitored during 2008–2011 in B. fuckeliana populations from both table-grape vineyards and greenhouse-grown strawberries in southern Italy. RESULTS Isolates showing different levels of resistance to anilinopyrimidines (APs) were detected at high frequency (up to 98%) in fields treated intensively with APs (4–7 sprays season−1). A slight decrease in sensitivity to fludioxonil, always combined with AP resistance, was generally found at lower frequencies. The repeated use of fenhexamid on grapevine (3–8 sprays season−1) led to a strong selection of highly resistant isolates (up to 100%). Boscalid-resistant mutants were detected at very variable frequencies (0–73%). Occurrence of resistance to quinone outside inhibitors (QoIs) was also ascertained. Multiple fungicide resistance to 2–6 different modes of action were frequently recovered. Single nucleotide polymorphisms (SNPs) in the target genes Erg27, SdhB and cytb were associated with resistance to fenehexamid, boscalid and QoIs respectively. CONCLUSION Resistance to the fungicides commonly used against grey mould on table grape and strawberry is quite common in southern Italy. This is an outcome of the incorrect use of fungicides, often because of the maximum number of detectable residues of plant protection products imposed by big international retailers, and underlines the crucial role of antiresistance strategies in integrated pest management. © 2013 Society of Chemical Industry
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molecular characterisation and detection of resistance to succinate dehydrogenase inhibitor fungicides in Botryotinia fuckeliana botrytis cinerea
Pest Management Science, 2014Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, Stefania Pollastro, C Rotolo, Francesco FaretraAbstract:BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs), interfering with fungal respiration, are considered to be fungicides at medium to high risk of resistance. Boscalid was the first molecule belonging to the SDHIs that was introduced for the control of Botryotinia fuckeliana. A range of different target-site mutations leading to boscalid resistance have been found in field populations of the fungus. The different types of mutation confer different cross-resistance profiles towards novel SDHIs, such as the recently introduced fungicide fluopyram. This study combines the determination of cross-resistance profiles and the setting-up of methods for fast molecular detection of the mutations. RESULTS: By means of in vitro tests, a range of SdhB mutations were characterised for resistance levels towards boscalid and fluopyram. SdhB mutations conferring P225L and P225F substitutions conferred high resistance to boscalid and high or moderate resistance to fluopyram respectively. Mutants carrying the N230I replacement were moderately resistant to both SDHIs. Substitutions at position H272 responsible for a high level of resistance to boscalid conferred sensitivity (H272R), hypersensitivity (H272Y) or moderate resistance (H272V) to fluopyram. Allele-specific (AS) PCR was developed and used for genotyping 135 B. fuckeliana isolates. The assay confirmed the strict association between resistance profiles and allelic variants of the SdhB gene. Real-time AS-PCR proved to be sensitive and specific for quantitative detection of different SDHI-resistant genotypes. CONCLUSION: Fluopyram-resistant mutants are currently rarely detected in the field sprayed with boscalid, but this may change with intensive exposure of the fungal population to fluopyram. PCR assays/methods developed in the study provide tools for fast monitoring of field populations and observing possible changes in population composition following fluopyram introduction, useful for the setting-up of appropriate preventive measures. © 2014 Society of Chemical Industry
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genetic analysis and molecular characterisation of laboratory and field mutants of Botryotinia fuckeliana botrytis cinerea resistant to qoi fungicides
Pest Management Science, 2012Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, Stefania Pollastro, C Rotolo, Hideo Ishii, Francesco FaretraAbstract:BACKGROUND: QoI fungicides, inhibitors of mitochondrial respiration, are considered to be at high risk of resistance development. In several phytopathogenic fungi, resistance is caused by mutations (most frequently G143A) in the mitochondrial cytochrome b (cytb) gene. The genetic and molecular basis of QoI resistance were investigated in laboratory and field mutants of Botryotinia fuckeliana (de Bary) Whetz. exhibiting in vitro reduced sensitivity to trifloxystrobin. RESULTS: B. fuckeliana mutants highly resistant to trifloxystrobin were obtained in the laboratory by spontaneous mutations in wild-type strains, or from naturally infected plants on a medium amended with 1–3 mg L−1 trifloxystrobin and 2 mM salicylhydroxamic acid, an inhibitor of alternative oxidase. No point mutations were detected, either in the complete nucleotide sequences of the cytb gene or in those of the aox and Rieske protein genes of laboratory mutants, whereas all field mutants carried the G143A mutation in the mitochondrial cytb gene. QoI resistance was always maternally inherited in ascospore progeny of sexual crosses of field mutants with sensitive reference strains. CONCLUSIONS: The G143A mutation in cytb gene is confirmed to be responsible for field resistance to QoIs in B. fuckeliana. Maternal inheritance of resistance to QoIs in progeny of sexual crosses confirmed that it is caused by extranuclear genetic determinants. In laboratory mutants the heteroplasmic state of mutated mitochondria could likely hamper the G143A detection, otherwise other gene(s) underlying different mechanisms of resistance could be involved. Copyright © 2012 Society of Chemical Industry
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Selection, characterization and genetic analysis of laboratory mutants of Botryotinia fuckeliana (Botrytis cinerea) resistant to the fungicide boscalid
European Journal of Plant Pathology, 2010Co-Authors: Rita Milvia De Miccolis Angelini, Stefania Pollastro, Caterina Rotolo, Wassim Habib, Francesco FaretraAbstract:Resistance to the fungicide boscalid in laboratory mutants of Botryotinia fuckeliana ( Botrytis cinerea ) was investigated. The baseline sensitivity to boscalid was evaluated in terms of colony growth (EC_50 = 0.3–3 µg ml^−1; MIC = 10–30 µg ml^−1) and conidial germination (EC_50 = 0.03–0.1 µg ml^−1; MIC = 1–3 µg ml^−1) tests. Mutants were selected in vitro from wild-type strains of the fungus on a fungicide-amended medium containing acetate as a carbon source. Mutants showed two different levels of resistance to boscalid, distinguishable through the conidial germination tests: low (EC_50 ∼ 0.3 µg ml^−1, ranging from 0.03 to 1 µg ml^−1; MIC > 100 µg ml^−1) and high (EC_50 > 100 µg ml^−1) resistance. Analysis of meiotic progeny from crosses between resistant mutants and sensitive reference strains showed that resistant phenotypes were due to mutations in single major gene(s) inherited in a Mendelian fashion, and linked with both the Daf1 and Mbc1 genes, responsible for resistance to dicarboximide and benzimidazole fungicides, respectively. Gene sequence analysis of the four sub-units of the boscalid-target protein, the succinate dehydrogenase enzyme, revealed that single or double point mutations in the highly conserved regions of the iron-sulphur protein (Ip) gene were associated with resistance. Mutations resulted in proline to leucine or phenylalanine replacements at position 225 (P225L or P225F) in high resistant mutants, and in a histidine to tyrosine replacement at position 272 (H272Y) in low resistant mutants. Sequences of the flavoprotein and the two transmembrane sub-units of succinate dehydrogenase were never affected.
Stefania Pollastro - One of the best experts on this subject based on the ideXlab platform.
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effects of polysaccharides from Botryotinia fuckeliana botrytis cinerea on in vitro culture of table and wine grapes vitis vinifera
Vitis: Journal of Grapevine Research, 2015Co-Authors: G Fanizza, Stefania Pollastro, V Bisignano, Monica Marilena Miazzi, Francesco FaretraAbstract:Shoots of several table and wine grape cultivars were cultured in vitro on a medium supplemented with polysaccharides obtained from a culture filtrate of Botryotinia fuckeliana through differential ethanolic precipitations. The general effects of polysaccharides resulted in leaf yellowness and in a reduction of fresh and dry weight. Differential response of assayed cultivars to polysaccharides seemed to be not related to their bunch susceptibility to grey mould under field conditions.
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occurrence of fungicide resistance in populations of Botryotinia fuckeliana botrytis cinerea on table grape and strawberry in southern italy
Pest Management Science, 2014Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, D Gerin, Stefania Pollastro, Caterina Rotolo, Francesco FaretraAbstract:BACKGROUND Botryotinia fuckeliana (Botrytis cinerea) is a pathogen with a high risk of development of resistance to fungicides. Fungicide resistance was monitored during 2008–2011 in B. fuckeliana populations from both table-grape vineyards and greenhouse-grown strawberries in southern Italy. RESULTS Isolates showing different levels of resistance to anilinopyrimidines (APs) were detected at high frequency (up to 98%) in fields treated intensively with APs (4–7 sprays season−1). A slight decrease in sensitivity to fludioxonil, always combined with AP resistance, was generally found at lower frequencies. The repeated use of fenhexamid on grapevine (3–8 sprays season−1) led to a strong selection of highly resistant isolates (up to 100%). Boscalid-resistant mutants were detected at very variable frequencies (0–73%). Occurrence of resistance to quinone outside inhibitors (QoIs) was also ascertained. Multiple fungicide resistance to 2–6 different modes of action were frequently recovered. Single nucleotide polymorphisms (SNPs) in the target genes Erg27, SdhB and cytb were associated with resistance to fenehexamid, boscalid and QoIs respectively. CONCLUSION Resistance to the fungicides commonly used against grey mould on table grape and strawberry is quite common in southern Italy. This is an outcome of the incorrect use of fungicides, often because of the maximum number of detectable residues of plant protection products imposed by big international retailers, and underlines the crucial role of antiresistance strategies in integrated pest management. © 2013 Society of Chemical Industry
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molecular characterisation and detection of resistance to succinate dehydrogenase inhibitor fungicides in Botryotinia fuckeliana botrytis cinerea
Pest Management Science, 2014Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, Stefania Pollastro, C Rotolo, Francesco FaretraAbstract:BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs), interfering with fungal respiration, are considered to be fungicides at medium to high risk of resistance. Boscalid was the first molecule belonging to the SDHIs that was introduced for the control of Botryotinia fuckeliana. A range of different target-site mutations leading to boscalid resistance have been found in field populations of the fungus. The different types of mutation confer different cross-resistance profiles towards novel SDHIs, such as the recently introduced fungicide fluopyram. This study combines the determination of cross-resistance profiles and the setting-up of methods for fast molecular detection of the mutations. RESULTS: By means of in vitro tests, a range of SdhB mutations were characterised for resistance levels towards boscalid and fluopyram. SdhB mutations conferring P225L and P225F substitutions conferred high resistance to boscalid and high or moderate resistance to fluopyram respectively. Mutants carrying the N230I replacement were moderately resistant to both SDHIs. Substitutions at position H272 responsible for a high level of resistance to boscalid conferred sensitivity (H272R), hypersensitivity (H272Y) or moderate resistance (H272V) to fluopyram. Allele-specific (AS) PCR was developed and used for genotyping 135 B. fuckeliana isolates. The assay confirmed the strict association between resistance profiles and allelic variants of the SdhB gene. Real-time AS-PCR proved to be sensitive and specific for quantitative detection of different SDHI-resistant genotypes. CONCLUSION: Fluopyram-resistant mutants are currently rarely detected in the field sprayed with boscalid, but this may change with intensive exposure of the fungal population to fluopyram. PCR assays/methods developed in the study provide tools for fast monitoring of field populations and observing possible changes in population composition following fluopyram introduction, useful for the setting-up of appropriate preventive measures. © 2014 Society of Chemical Industry
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genetic analysis and molecular characterisation of laboratory and field mutants of Botryotinia fuckeliana botrytis cinerea resistant to qoi fungicides
Pest Management Science, 2012Co-Authors: Rita Milvia De Miccolis Angelini, Mario Masiello, Stefania Pollastro, C Rotolo, Hideo Ishii, Francesco FaretraAbstract:BACKGROUND: QoI fungicides, inhibitors of mitochondrial respiration, are considered to be at high risk of resistance development. In several phytopathogenic fungi, resistance is caused by mutations (most frequently G143A) in the mitochondrial cytochrome b (cytb) gene. The genetic and molecular basis of QoI resistance were investigated in laboratory and field mutants of Botryotinia fuckeliana (de Bary) Whetz. exhibiting in vitro reduced sensitivity to trifloxystrobin. RESULTS: B. fuckeliana mutants highly resistant to trifloxystrobin were obtained in the laboratory by spontaneous mutations in wild-type strains, or from naturally infected plants on a medium amended with 1–3 mg L−1 trifloxystrobin and 2 mM salicylhydroxamic acid, an inhibitor of alternative oxidase. No point mutations were detected, either in the complete nucleotide sequences of the cytb gene or in those of the aox and Rieske protein genes of laboratory mutants, whereas all field mutants carried the G143A mutation in the mitochondrial cytb gene. QoI resistance was always maternally inherited in ascospore progeny of sexual crosses of field mutants with sensitive reference strains. CONCLUSIONS: The G143A mutation in cytb gene is confirmed to be responsible for field resistance to QoIs in B. fuckeliana. Maternal inheritance of resistance to QoIs in progeny of sexual crosses confirmed that it is caused by extranuclear genetic determinants. In laboratory mutants the heteroplasmic state of mutated mitochondria could likely hamper the G143A detection, otherwise other gene(s) underlying different mechanisms of resistance could be involved. Copyright © 2012 Society of Chemical Industry
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Selection, characterization and genetic analysis of laboratory mutants of Botryotinia fuckeliana (Botrytis cinerea) resistant to the fungicide boscalid
European Journal of Plant Pathology, 2010Co-Authors: Rita Milvia De Miccolis Angelini, Stefania Pollastro, Caterina Rotolo, Wassim Habib, Francesco FaretraAbstract:Resistance to the fungicide boscalid in laboratory mutants of Botryotinia fuckeliana ( Botrytis cinerea ) was investigated. The baseline sensitivity to boscalid was evaluated in terms of colony growth (EC_50 = 0.3–3 µg ml^−1; MIC = 10–30 µg ml^−1) and conidial germination (EC_50 = 0.03–0.1 µg ml^−1; MIC = 1–3 µg ml^−1) tests. Mutants were selected in vitro from wild-type strains of the fungus on a fungicide-amended medium containing acetate as a carbon source. Mutants showed two different levels of resistance to boscalid, distinguishable through the conidial germination tests: low (EC_50 ∼ 0.3 µg ml^−1, ranging from 0.03 to 1 µg ml^−1; MIC > 100 µg ml^−1) and high (EC_50 > 100 µg ml^−1) resistance. Analysis of meiotic progeny from crosses between resistant mutants and sensitive reference strains showed that resistant phenotypes were due to mutations in single major gene(s) inherited in a Mendelian fashion, and linked with both the Daf1 and Mbc1 genes, responsible for resistance to dicarboximide and benzimidazole fungicides, respectively. Gene sequence analysis of the four sub-units of the boscalid-target protein, the succinate dehydrogenase enzyme, revealed that single or double point mutations in the highly conserved regions of the iron-sulphur protein (Ip) gene were associated with resistance. Mutations resulted in proline to leucine or phenylalanine replacements at position 225 (P225L or P225F) in high resistant mutants, and in a histidine to tyrosine replacement at position 272 (H272Y) in low resistant mutants. Sequences of the flavoprotein and the two transmembrane sub-units of succinate dehydrogenase were never affected.
Guizhen Peng - One of the best experts on this subject based on the ideXlab platform.
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botryotins a h tetracyclic diterpenoids representing three carbon skeletons from a deep sea derived Botryotinia fuckeliana
Organic Letters, 2020Co-Authors: Siwen Niu, Guizhen Peng, Chunlan Xie, Jinmei Xia, Qingmei Liu, Guangming Liu, Xianwen YangAbstract:Eight unprecedent diterpenoids, botryotins A–H (1–8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2–6), and 6/6/6/5 (7 and 8) t...
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a new pimarane diterpenoid from the Botryotinia fuckeliana fungus isolated from deep sea water
Chemistry & Biodiversity, 2019Co-Authors: Siwen Niu, Guizhen Peng, Chunlan Xie, Jinmei Xia, Xianwen YangAbstract:A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20 μm).
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aphidicolin chemistry of the deep sea derived fungus Botryotinia fuckeliana mccc 3a00494
Journal of Natural Products, 2019Co-Authors: Zengpeng Li, Zhiwei Yi, Guizhen Peng, Longhe Yang, Zongze Shao, Xianwen YangAbstract:Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1–A71, 1–71) and eight known (72–79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (−5572 m). The structures of 1–71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher’s method, and the ECD exciton chirality method. Compounds 54–57 and 58–64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65–71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 μM) and HL-60 (IC50 = 6.1 μM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to...
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aphidicolin chemistry of the deep sea derived fungus Botryotinia fuckeliana mccc 3a00494
Journal of Natural Products, 2019Co-Authors: Siwen Niu, Guizhen Peng, Longhe Yang, Zongze Shao, Chunlan Xie, Jinmei Xia, Zhuhua Luo, Xianwen YangAbstract:Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 μM) and HL-60 (IC50 = 6.1 μM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.
Pierre Leroux - One of the best experts on this subject based on the ideXlab platform.
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the hydroxyanilide fenhexamid a new sterol biosynthesis inhibitor fungicide efficient against the plant pathogenic fungus Botryotinia fuckeliana botrytis cinerea
Pest Management Science, 2001Co-Authors: Daniele Debieu, Jocelyne Bach, Mickael Hugon, Christian Malosse, Pierre LerouxAbstract:Fenhexamid, a recently developed botryticide, is shown here to inhibit sterol biosynthesis. When the fungus Botryotinia fuckeliana was grown in the presence of fenhexamid, the ergosterol content was reduced, and three 3-keto compounds, 4α-methylfecosterone, fecosterone and episterone, accumulated, suggesting an inhibition of the 3-keto reductase involved in C-4 demethylation. Thus, fenhexamid belongs to a new, promising class of sterol biosynthesis inhibitors not previously used in agriculture or in medicine. © 2001 Society of Chemical Industry
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patterns of cross resistance to fungicides in Botryotinia fuckeliana botrytis cinerea isolates from french vineyards
Crop Protection, 1999Co-Authors: Pierre Leroux, Florence Chapeland, Denis Desbrosses, Michel GredtAbstract:Abstract Field strains of Botryotinia fuckeliana were isolated from diseased grape berries which were collected at the harvest, between 1993 and 1997, from French vineyards located in Alsace, Armagnac, Bordeaux, Champagne and Loire Valley. According to the inhibitory effects of fungicides towards spore germination, germ-tube elongation and mycelial growth, several phenotypes could be characterized. Thus, two types of benzimidazole (e.g. carbendazim, thiabendazole)-resistant strains were detected; negative cross-resistance towards diethofencarb, diphenylamine and dicloran was found only in one type. Most dicarboximide (e.g. iprodione, procymidone, vinclozolin)-resistant strains were also weakly resistant to aromatic hydrocarbon fungicides (e.g. chloroneb, dicloran, tolclofos-methyl) but remained sensitive to phenylpyrroles (e.g. fenpiclonil, fludioxonil). However, in some other dicarboximide-resistant strains, resistance was observed either as being restricted to dicarboximides or as extending weakly to phenylpyrroles. Towards anilinopyrimidines (e.g. cyprodinil, mepanipyrim, pyrimethanil), three resistant phenotypes have been identified. In the most resistant one, resistance was restricted to anilinopyrimidines, whereas in the others, resistance extended to various other groups of fungicides including dicarboximides, phenylpyrroles, sterol biosynthesis inhibitors (e.g. tolfanate, prochloraz, tebuconazole) and the hydroxyanilide derivative, fenhexamid. According to the pattern of cross-resistance, two phenotypes were characterized within these multifungicide-resistant strains. In vitro tests conducted with fenpropimorph, fenpropidin and spiroxamine, revealed the existence of strains highly susceptible to these sterol Δ14- reduction inhibitors. This property was correlated with a decreased sensitivity towards fenhexamid.
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inheritance and mechanisms of resistance to anilinopyrimidine fungicides in botrytis cinerea Botryotinia fuckeliana
Pesticide Biochemistry and Physiology, 1999Co-Authors: Michel Gredt, Florence Chapeland, Rene Fritz, Catherine Lanen, Pierre LerouxAbstract:Abstract Monitoring conducted in French vineyards since 1994 led to detection of three anilinopyrimidine-resistant phenotypes in field populations of Botrytis cinerea ( Botryotinia fuckeliana ). A few strains were highly resistant to anilinopyrimidines (e.g., pyrimethanil) only and were named Ani R1 . Analysis of tetrads obtained from crosses between Ani R1 and sensitive strains (Ani S ) showed that one major gene is probably involved in the Ani R1 phenotype. The resistance mechanism has not yet been elucidated but the Ani R1 strains did not seem to display a reduced accumulation of [ 14 C]pyrimethanil in their mycelium. We also distinguished two different patterns of cross-resistance, named Ani R2 and Ani R3 phenotypes. Both were weakly resistant to anilinopyrimidines, highly resistant to tolnaftate, a squalene epoxidase inhibitor (used only in medicine), and appeared less sensitive to dicarboximides (e.g., iprodione). Moreover, Ani R2 strains were weakly resistant to phenylpyrroles (e.g., fludioxonil) while Ani R3 strains displayed a slight decrease of sensitivity to sterol C14-demethylation inhibitors (e.g., prochloraz, tebuconazole) and to the experimental hydroxyanilide fenhexamid. Genetic analysis showed that there is no disjunction of multiple resistances in ascospore progenies and we found a 1:1 segregation of sensitive:resistant phenotypes, suggesting that Ani R2 and Ani R3 phenotypes are each probably encoded by a single major gene. Studies on the uptake of [ 14 C]pyrimethanil did not show any difference between the sensitive and the resistant strains. However, the addition of fluazinam, an uncoupler, led to an accumulation of the fungicide in mycelium, suggesting that an active efflux occurred. Experiments carried out on the uptake of [ 14 C]tebuconazole and [ 14 C]triadimenol, two sterol C14-demethylation inhibitors, showed a lower accumulation of these fungicides in mycelium of resistant strains than in sensitive strains. The effect of fluazinam demonstrated that this phenomenon was correlated with an energy-dependent efflux, which seemed to be inducible in sensitive strains and constitutive in resistant strains and could be a multidrug resistance mechanism.