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15 pages, 5440 KB

Open AccessArticle

Insight into the Structure of Antifungal Cyrmenins: Conformational Studies of Unique Dehydroamino Acid, O-Methyldehydroserine

by Karolina Banaś, Paweł Lenartowicz, Monika Staś-Bobis, Błażej Dziuk and Dawid Siodłak

Int. J. Mol. Sci. 2025, 26(1), 340; https://doi.org/10.3390/ijms26010340 - 2 Jan 2025

Cited by 1 | Viewed by 1404

Abstract

O-Methyldehydroserine, ΔSer(Me), is a non-standard α,β-dehydroamino acid, which occurs naturally in Cyrmenins with potential pharmaceutical application. The C-terminal part and the side chain of the ΔSer(Me) residue constitute the β-methoxyacrylate unit, responsible for antifungal activity of Cyrmenins. The short model, Ac-ΔSer(Me)-OMe, was analyzed [...] Read more.

O-Methyldehydroserine, ΔSer(Me), is a non-standard α,β-dehydroamino acid, which occurs naturally in Cyrmenins with potential pharmaceutical application. The C-terminal part and the side chain of the ΔSer(Me) residue constitute the β-methoxyacrylate unit, responsible for antifungal activity of Cyrmenins. The short model, Ac-ΔSer(Me)-OMe, was analyzed considering the geometrical isomer Z (1) and E (2). The Ramachandran diagrams were created for both isomers, using quantum chemical calculations, to show possible conformations for isolated molecules (in vacuo), in weakly polar (chloroform) and polar (water) environments. The Ac-(Z)-ΔSer(Me)-OMe (1) was synthesized and the single-crystal X-ray diffraction analysis together with FT-IR spectra were performed. The detailed analysis of the conformations of the (Z)-ΔSer(Me) residue is presented considering the intra- and intermolecular interactions as well as their influence on the β-methoxyacrylate part. It is concluded that the β-methoxyacrylate structural motif is able to maintain a planar geometry, crucial for biological activity, regardless of the conformation adopted by O-methyldehydroserine. Full article

(This article belongs to the Section Molecular Pharmacology)

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16 pages, 2357 KB

Open AccessArticle

Dissipation, Residue and Human Dietary Risk Assessment of Pyraclostrobin and Cyazofamid in Grapes Using an HPLC-UV Detector

by Peiying Zhao, Rong Liu and Longfei Yuan

Foods 2024, 13(2), 314; https://doi.org/10.3390/foods13020314 - 18 Jan 2024

Cited by 4 | Viewed by 2710

Abstract

Pyraclostrobin is a new broad-spectrum methoxyacrylic acid fungicide. Cyazofamid is a new selective foliar spray acaricide. Here, we studied the degradation rate and final residues of pyraclostrobin and cyazofamid in grape and evaluated their dietary risk to consumers. The average recoveries of pyraclostrobin [...] Read more.

Pyraclostrobin is a new broad-spectrum methoxyacrylic acid fungicide. Cyazofamid is a new selective foliar spray acaricide. Here, we studied the degradation rate and final residues of pyraclostrobin and cyazofamid in grape and evaluated their dietary risk to consumers. The average recoveries of pyraclostrobin ether ester, cyazofamid and cyazofamid metabolite (CCIM) in grapes were 84–94%, 92–98% and 99–104%, respectively. The relative standard deviations (RSDs) were 6.0–20.3%, 2.4–10.5% and 1.3–4.0%, respectively, and the LOQs were all 0.05 mg/kg. The digestion dynamics of the experimental sites were in accordance with the first-order kinetic equation. The degradation half-lives of pyraclostrobin ether ester and cyazofamid were 17.8 d–28.9 d and 4.3 d–7.8 d, respectively. The final residues of pyraclostrobin ether ester, cyazofamid and CCIM in grapes were <0.05–1.88 mg/kg, <0.05–0.31 mg/kg and <0.05–0.47 mg/kg, respectively. Using probability models, the total chronic risk values for pyraclostrobin and cyazofamid were calculated to be 0.112–189.617% and 0.021–1.714%, respectively. The results of the contribution analysis indicate that pyraclostrobin poses a much greater risk to Chinese consumers than cyazofamid, especially to children and adolescents, who have a significantly greater risk than adults. This suggests that more consideration should be given to the cumulative risk of compounds for vulnerable groups in the future. Full article

(This article belongs to the Special Issue Risk Assessment and Dietary Exposure of Hazardous Substances in Foods)

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17 pages, 3621 KB

Open AccessArticle

Synthesis and Antifungal Activity of New butenolide Containing Methoxyacrylate Scaffold

by Qian Zhang, Yihao Li, Bin Zhao, Leichuan Xu, Haoyun Ma and Mingan Wang

Molecules 2022, 27(19), 6541; https://doi.org/10.3390/molecules27196541 - 3 Oct 2022

Cited by 6 | Viewed by 2666

Abstract

In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by ¹H NMR, ¹³C NMR, [...] Read more.

In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by ¹H NMR, ¹³C NMR, HR-MS spectra, and X-ray diffraction analysis. The in vitro antifungal activities were evaluated by the mycelium growth rate method. The results showed that the inhibitory activities of these new compounds against Sclerotinia sclerotiorum were significantly improved, in comparison with that of the lead compound 3–8; the EC₅₀ values of V-6 and VI-7 against S. sclerotiorum were 1.51 and 1.81 mg/L, nearly seven times that of 3–8 (EC₅₀ 10.62 mg/L). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound VI-3 had a significant impact on the structure and function of the hyphal cell of S. sclerotiorum mycelium and the positive control trifloxystrobin. Molecular simulation docking results indicated that the introduction of methoxyacrylate scaffold is beneficial to improving the antifungal activity of these compounds against S. sclerotiorum, which can be used as the lead for further structure optimization. Full article

(This article belongs to the Special Issue Natural Products and Their Semi-synthetic Derivatives against Bacteria, Fungi, and Parasites II)

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28 pages, 9936 KB

Open AccessReview

Natural Compound-Derived Cytochrome bc1 Complex Inhibitors as Antifungal Agents

by Loana Musso, Andrea Fabbrini and Sabrina Dallavalle

Molecules 2020, 25(19), 4582; https://doi.org/10.3390/molecules25194582 - 7 Oct 2020

Cited by 38 | Viewed by 6771

Abstract

The high incidence of fungal pathogens has become a global issue for crop protection. A promising strategy to control fungal plant infections is based on the use of nature-inspired compounds. The cytochrome bc1 complex is an essential component of the cellular respiratory chain [...] Read more.

The high incidence of fungal pathogens has become a global issue for crop protection. A promising strategy to control fungal plant infections is based on the use of nature-inspired compounds. The cytochrome bc1 complex is an essential component of the cellular respiratory chain and is one of the most important fungicidal targets. Natural products have played a crucial role in the discovery of cytochrome bc1 inhibitors, as proven by the development of strobilurins, one of the most important classes of crop-protection agents, over the past two decades. In this review, we summarize advances in the exploration of natural product scaffolds for the design and development of new bc1 complex inhibitors. Particular emphasis is given to molecular modeling-based approaches and structure–activity relationship (SAR) studies performed to improve the stability and increase the potency of natural precursors. The collected results highlight the versatility of natural compounds and provide an insight into the potential development of nature-inspired derivatives as antifungal agents. Full article

(This article belongs to the Special Issue Design of Natural Products Lead Molecules Using Organic Synthesis)

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12 pages, 1294 KB

Open AccessArticle

Design, Synthesis, and Acaricidal Activity of Phenyl Methoxyacrylates Containing 2-Alkenylthiopyrimidine

by Shulin Hao, Zengfei Cai, Yangyang Cao and Xiaohua Du

Molecules 2020, 25(15), 3379; https://doi.org/10.3390/molecules25153379 - 25 Jul 2020

Cited by 16 | Viewed by 3954

Abstract

A series of novel phenyl methoxyacrylate derivatives containing a 2-alkenylthiopyrimidine substructure were designed, synthesized, and evaluated in terms of acaricidal activity. The structures of the title compounds were identified by ¹H NMR, ¹³C NMR and high-resolution mass spectra (HRMS). Compound ( [...] Read more.

A series of novel phenyl methoxyacrylate derivatives containing a 2-alkenylthiopyrimidine substructure were designed, synthesized, and evaluated in terms of acaricidal activity. The structures of the title compounds were identified by ¹H NMR, ¹³C NMR and high-resolution mass spectra (HRMS). Compound (E)-methyl 2-(2-((2-(3,3-dichloroallylthio)-6-(trifluoromethyl)pyrimidin-4-yloxy)methyl)phenyl)-3-methoxyacr-ylate (4j) exhibited significant acaricidal activity against Tetranychus cinnabarinus (T. cinnabarinus) in greenhouse tests possessing nearly twice the larvicidal and ovicidal activity compared to fluacrypyrim. Furthermore, the results of the field trials demonstrated that compound 4j could effectively control Panonychuscitri with long-lasting persistence and rapid action. The toxicology data in terms of LD₅₀ value confirmed that compound 4j has a relatively low acute toxicity to mammals, birds, and honeybees. Full article

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14 pages, 2497 KB

Open AccessArticle

Identification of Azoxystrobin Glutathione Conjugate Metabolites in Maize Roots by LC-MS

by Giuseppe Dionisio, Maheswor Gautam and Inge Sindbjerg Fomsgaard

Molecules 2019, 24(13), 2473; https://doi.org/10.3390/molecules24132473 - 5 Jul 2019

Cited by 10 | Viewed by 6482

Abstract

Xenobiotic detoxification in plant as well as in animals has mostly been studied in relationship to the deactivation of the toxic residues of the compound that, surely for azoxystrobin, is represented by its β-methoxyacrylate portion. In maize roots treated for 96 h with [...] Read more.

Xenobiotic detoxification in plant as well as in animals has mostly been studied in relationship to the deactivation of the toxic residues of the compound that, surely for azoxystrobin, is represented by its β-methoxyacrylate portion. In maize roots treated for 96 h with azoxystrobin, the fungicide accumulated over time and detoxification compounds or conjugates appeared timewise. The main detoxified compound was the methyl ester hydrolysis product (azoxystrobin free acid, 390.14 m/z) thought to be inactive followed by the glutathione conjugated compounds identified as glutathione conjugate (711.21 m/z) and its derivative lacking the glycine residue from the GSH (654.19 m/z). The glycosylated form of azoxystrobin was also found (552.19 m/z) in a minor amount. The identification of these analytes was done by differential untargeted metabolomics analysis using Progenesis QI for label free spectral counting quantification and MS/MS confirmation of the compounds was carried out by either Data Independent Acquisition (DIA) and Data Dependent Acquisition (DDA) using high resolution LC-MS methods. Neutral loss scanning and comparison with MS/MS spectra of azoxystrobin by DDA and MSe confirmed the structures of these new azoxystrobin GSH conjugates. Full article

(This article belongs to the Special Issue (Mass Spectrometric) Non Target Screening–Techniques and Strategies)

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14 pages, 4145 KB

Open AccessArticle

Synthesis and Evaluation of Essential Oil-Derived β-Methoxyacrylate Derivatives as High Potential Fungicides

by Haihuan Su, Wenda Wang, Longzhu Bao, Shuangshuang Wang and Xiufang Cao

Molecules 2017, 22(5), 763; https://doi.org/10.3390/molecules22050763 - 8 May 2017

Cited by 9 | Viewed by 6743

Abstract

Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, [...] Read more.

Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, a series of essential oil-based β-methoxyacrylate derivatives have been designed and synthesized. The target compounds have been screened for their potential fungicidal activity against eleven species of plant pathogen fungi, including Alternaria alternata, Phomopsis adianticola, Pestalotiopsis theae, Sclerotinia sclerotiorum, etc. Compared with intermediates I, the parent essential oils and azoxystrobin, almost all of essential oil-based β-methoxyacrylate derivatives exhibited significantly better fungicidal activity. Further investigation revealed that some compounds showed remarkable inhibitory activities against Pestalotiopsis theae, Phomopsis adianticola, Sclerotinia sclerotiorum and Magnapothe grisea at different concentrations in contrast to the commercial product azoxystrobin. Compound II-8 exhibited particularly significant fungicidal activity. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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4 pages, 207 KB

Open AccessShort Note

Synthesis of 4,4'-(Cyclohexane-1,1-diyl)bis(1-methyl- 1H-pyrazol-5-ol)

by Gernot A. Eller and Wolfgang Holzer

Molbank 2008, 2008(2), M569; https://doi.org/10.3390/M569 - 22 Aug 2008

Cited by 1 | Viewed by 4824

Abstract

Methyl (2E)-3-methoxyacrylate and excess methylhydrazine yield crude 1- methyl-2-pyrazolin-5-one which is reacted with cyclohexanone to obtain the title compound in 86% yield. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, and MS) are presented. Full article

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