Recent Advances in Design and Development of Diazole and Diazine Based Fungicides (2014–2023)

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(28), P. 15427 - 15448

Published: July 5, 2024

With fungal diseases posing a major threat to agricultural production, the application of fungicides control related is often considered necessary ensure world's food supply. The search for new bioactive agents has long been priority in crop protection due continuous development resistance against currently used types active compounds. Heterocyclic compounds are an inseparable part core structures numerous lead compounds, these rings constitute pharmacophores significant number developed over past decade by agrochemists. Among heterocycles, nitrogen-based play essential role. To date, diazole (imidazole and pyrazole) diazine (pyrimidine, pyridazine, pyrazine) derivatives make up important series synthetic fungicides. In recent years, many reports have published on design, synthesis, study fungicidal activity scaffolds, but there was lack comprehensive classified review nitrogen-containing scaffolds. Regarding this issue, here we reviewed articles families. current review, molecules synthesized so far based size ring.

Language: Английский

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Regioselective [3 + 2] cycloaddition of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes: a facile access to 3-di/trifluoroalkyl-5-fluoropyrazoles

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(24), P. 5040 - 5045

Published: Jan. 1, 2023

We describe the base-mediated [3 + 2] cycloaddition reaction of di/trifluoromethylated hydrazonoyl chlorides with fluoronitroalkenes for synthesis densely functionalized 3-di/trifluoroalkyl-5-fluoropyrazoles potent biological activity.

Language: Английский

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Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 3, 2023

To promote the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we introduced cinnamamide and nicotinamide structural fragments into structure pyrazol-5-yl-amide by carbon chain extension scaffold hopping, respectively, synthesized a series derivatives. The results biological activity assays indicated that most target compounds exhibited varying degrees inhibitory against tested fungi. Notably, G22, G28, G34, G38, G39 excellent in vitro antifungal activities Valsa mali with EC50 values 0.48, 0.86, 0.57, 0.73, 0.87 mg/L, this result was significantly more potent than boscalid (EC50 = 2.80 mg/L) closer to specialty control drug tebuconazole 0.30 mg/L). Compounds G22 G34 also vivo protective curative effects V. at 40 mg/L. SEM TEM observations may affect normal mycelial morphology as well cellular ultrastructure. Molecular docking analysis possessed similar binding mode SDH, detailed SDH inhibition validated feasibility designed potential inhibitors. G3 were selected for theoretical calculations, terminal carboxylic acid group be key region influencing activity. Furthermore, toxicity tests on Apis mellifera l. revealed low A. populations. above demonstrated these pyrazole-5-yl-amide derivatives are promising low-risk drug-resistance SDHI fungicides.

Language: Английский

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Design, Synthesis, and Fungicidal Evaluation of Novel N-Methoxy Pyrazole-4-Carboxamides as Potent Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(5), P. 2610 - 2615

Published: Jan. 25, 2023

Succinate dehydrogenase (SDH, EC 1.3.5.1, also known as complex II) has been recognized one of the most promising targets fungicides. Here, based on binding mode pydiflumetofen with SDH, carbon-carbon double bond was introduced into chemical and then produced target compounds 6a-6o. The enzymatic inhibitory activity structure-activity relationship (SAR) study showed that 2-position 4-position in terminal benzene were positive to increasing activity. Furthermore, fungicidal results greenhouses indicated compound 6o good control effects against wheat powdery mildew (WPM), cucumber (CPM), southern corn rust (SCR), showing its broad-spectrum property. Especially, exhibited 95 75% CPM SCR at 6.25 mg/L, respectively, which are better than (80% 15% SCR), indicating potency is worthy further development.

Language: Английский

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Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(30), P. 11341 - 11349

Published: July 18, 2023

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying isoquinoline-3-hydrazide as antifungal scaffold. special practical potential this model demonstrated by phenotypic bioassay, molecular docking, cross-resistance evaluation. panel (LW2, LW3, LW11) acquired, showing much better performance than positive controls. Specifically, compound LW3 exhibited broad spectrum holding EC50 values low 0.54, 0.09, 1.52, 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , F. graminearum, respectively. It curative efficacy that boscalid in controlling plant disease caused cinerea. candidate did not show extensively used succinate dehydrogenase inhibitor (SDHI) fungicides can efficiently inhibit resistant cinerea strains. docking is quite different from controls fluopyram. This progress highlights practicality isoquinoline hydrazide fungicide

Language: Английский

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Design, Synthesis, and Antifungal Activities of Novel Potent Fluoroalkenyl Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(26), P. 14535 - 14546

Published: June 21, 2024

The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness fungicides in production. In this study, series novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated their antifungal activities against eight fungi. results from

Language: Английский

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Reversible Regulation of Succinate Dehydrogenase by Tools of Photopharmacology

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(14), P. 4279 - 4290

Published: March 31, 2022

Succinate dehydrogenase (SDH) is extremely important in metabolic function and biological processes. Modulation of SDH has been reported to be a promising therapeutic target mutations. Current measures for the regulation are scarce, precise reversible modulation still remains challenging. Herein, powerful tool optical control was proposed evaluated utilizing technology photopharmacology. We photochromic ligands (PCLs), azobenzene-pyrazole amides (APAs), that exert light-dependent inhibition effects on SDH. Physicochemical property tests assays were conducted demonstrate feasibility modulating In this paper, common agricultural pathogens used develop procedure by which our PCLs could reversibly precisely green light. This research would help us understand target-ligand interactions provide new insights into

Language: Английский

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Design, Synthesis, and Biological Evaluation of Novel Pyrazol-5-yl-benzamide Derivatives Containing Oxazole Group as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(43), P. 13839 - 13848

Published: Oct. 21, 2022

A series of pyrazol-5-yl-benzamide derivatives containing the oxazole group were designed and synthesized as potential SDH inhibitors. According to results bioassays, most target compounds displayed moderate-to-excellent in vitro antifungal activities against Valsa mali, Sclerotinia scleotiorum, Alternaria alternata, Botrytis cinerea. Among them, C13, C14, C16 exhibited more excellently inhibitory S. sclerotiorum than boscalid (EC50 = 0.96 mg/L), with EC50 values 0.69, 0.26, 0.95 mg/L, respectively. In vivo experiments on rape leaves cucumber showed that C13 C14 considerable protective effects boscalid. SEM analysis indicated significantly destroyed typical structure morphology scleotiorum hyphae. respiratory inhibition effect assays, (28.0%) (33.9%) a strong respiration rate mycelia, which was close (30.6%). The molecular docking could form interactions key residues TRP O:173, ARG P:43, TYR Q:58, MET P:43 SDH. Furthermore, mechanism these demonstrated by enzymatic assay. These demonstrate can be developed into novel inhibitors for crop protection.

Language: Английский

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Discovery of N-Methoxy-(biphenyl-ethyl)-pyrazole-carboxamides as Novel Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(45), P. 14480 - 14487

Published: Nov. 2, 2022

Succinate dehydrogenase (SDH) inhibitor is one of the research hotspots for development fungicides. Herein, we describe design and synthesis N-methoxy-(biphenyl-ethyl)-pyrazole-carboxamide derivatives with enhanced fungicidal activity by employing fragment combination strategy. The SDH enzymatic was evaluated 24 title compounds, compound 7s identified as highest against porcine an IC50 value 0.014 μM, 205-fold greater than that fluxapyroxad. Furthermore, greenhouse experiments showed 7u exhibited potent wheat powdery mildew EC50 0.633 mg/L, higher fluxapyroxad benzovindiflupyr. computational results fluorine atom substituted on pyrazole ring formed extra dipolar–dipolar interaction C_S42 then increased van der Waals between SDH. structural mechanistic insights obtained from present work will provide a valuable clue to developing novel inhibitors.

Language: Английский

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Discovery of Novel Pyrazol-5-yl-benzamide Derivatives Containing a Thiocyanato Group as Broad-Spectrum Fungicidal Candidates

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(46), P. 17700 - 17712

Published: Nov. 8, 2023

In an effort to promote the development of new fungicides, a series 48 novel N-(1-methyl-4-thiocyanato-1H-pyrazol-5-yl)-benzamide derivatives A1-A36 and B1-B12 were designed synthesized by incorporating thiocyanato group into pyrazole ring, their fungicidal activities evaluated against Sclerotinia sclerotiorum, Valsa mali, Botrytis cinerea, Rhizoctonia solani, Phytophthora capsici. in vitro antifungal/antioomycete assay, many target compounds exhibited good broad-spectrum activities. Among them, compound A36 displayed best antifungal activity V. mali with EC50 value 0.37 mg/L, which was significantly higher than that positive controls fluxapyroxad (13.3 mg/L) dimethomorph (10.3 mg/L). Meanwhile, B6 antioomycete P. capsici 0.41 azoxystrobin (29.2 but lower (0.13 Notably, A27 inhibitory B. R. S. respective values 0.71, 1.44, 1.78, 0.87, 1.61 mg/L. The vivo experiments revealed presented excellent protective curative efficacies capsici, similar control dimethomorph. Scanning electron microscopy (SEM) transmission (TEM) analyses showed could change mycelial morphology severely damage ultrastructure results SDH enzymatic inhibition indicated effectively inhibit (PcSDH). Furthermore, molecular docking analysis demonstrated significant hydrogen bonds Pi-S bonding between key amino acid residues PcSDH, explain probable mechanism action. Collectively, these studies provide valuable approach expanding spectrum pyrazol-5-yl-benzamide derivatives.

Language: Английский

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