Molecular topology and QSAR multi-target analysis to boost the in silico research for fungicides in agricultural chemistry

Zanni, Riccardo; Gálvez-Llompart, María; García-Pereira, Inma; Gálvez, Jorge; García-Domènech, Ramón

doi:10.1007/s11030-018-9879-3

Cited by 7 publications

(16 citation statements)

References 23 publications

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“…mali (EC 50 = 11.7 mg/L) . Additionally, the diphenylamine scaffold has been widely used in drug design, and its derivatives have exhibited a broad spectrum of biological activities, such as antiproliferative, anti-inflammatory, antifungal, insecticidal, acaricidal, rodenticidal, and herbicidal activities. − …”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

Ma,

Zhou,

Lin

et al. 2024

J. Agric. Food Chem.

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To accelerate the development of novel fungicides, a variety of N- (pyrazol-5-yl)benzamide derivatives with a diphenylamine moiety were designed and synthesized using a pharmacophore recombination strategy based on the structure of pyrazol-5-yl-aminophenyl-benzamides. The bioassay results demonstrated that most of the target compounds had excellent in vitro antifungal activities against Sclerotinia sclerotiorum, Valsa mali, and Botrytis cinerea. In particular, compound 5IIIh exhibited remarkable activity against S. sclerotiorum (EC 50 = 0.37 mg/L), which was similar to that of fluxapyroxad (EC 50 = 0.27 mg/L). In addition, compound 5IIIc (EC 50 = 1.32 mg/L) was observed to be more effective against V. mali than fluxapyroxad (EC 50 = 12.8 mg/L) and comparable to trifloxystrobin (EC 50 = 1.62 mg/L). Furthermore, compound 5IIIh demonstrated remarkable in vivo protective antifungal properties against S. sclerotiorum, with an inhibition rate of 96.8% at 100 mg/L, which was close to that of fluxapyroxad (99.6%). Compounds 5IIIc (66.7%) and 5IIIh (62.9%) exhibited good in vivo antifungal effects against V. mali at 100 mg/L, which were superior to that of fluxapyroxad (11.1%) but lower than that of trifloxystrobin (88.9%). The succinate dehydrogenase (SDH) enzymatic inhibition assay was conducted to confirm the mechanism of action. Molecular docking analysis further revealed that compound 5IIIh has significant hydrogen-bonding, π−π, and p−π conjugation interactions with ARG 43, SER 39, TRP 173, and TYR 58 in the binding site of SDH, and the binding mode was similar to that of the commercial fungicide fluxapyroxad. All of the results suggest that compound 5IIIh could be a potential SDH inhibitor, offering a valuable reference for future studies.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

Ma,

Zhou,

Lin

et al. 2024

J. Agric. Food Chem.

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“…This work constitutes a demonstration of SSIR performance by analyzing a group of 40 diphenylamine derivatives, i.e., a family of congeneric derivatives that share the same molecular skeleton or scaffold. The set has been taken from reference [4], which, in turn, collects data from references [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Zanni et al [4] published an interesting work that, using molecular topological indices treated with linear discriminant analysis, led to the classification of diphenylamine derivatives as fungicides against three species (cucumber downy mildew, rice blast and cucumber gray mold). The approach was based on the generation of molecules from a common scaffold.…”

Section: Introductionmentioning

confidence: 99%

Application of SSIR Method for the Design of Fungicides

Julián-Ortiz

Besalú

2023

Applied Sciences

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The design of fungicides is a central topic in agricultural chemistry. In this manuscript, it is shown how the Superposition of Significant Interaction Rules (SSIR) method can serve the generation of new potentially active molecules. By using SSIR, it is shown how the process becomes a simple symbolic procedure without the intervention of sophisticated statistical methods, although the results obtained are comparable.

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“…The methodology allows a fast and precise prediction of many biological and physicochemical properties. − Defined as a part of mathematical chemistry, MT is related to the assimilation between molecules and graphs, , so that it can depict molecular structures through graph theoretical indices. , Besides, it deals with the connectivity of atoms in molecules and not with geometrical features such as angles, distances, or tridimensional structures, which are common in standard/conventional approaches. , This way, graph theory and surrounding disciplines stand as basic tools for MT development. By this approach, excellent results have been obtained in the design and selection of new drugs for different pharmacological fields − and more recently in crop protection. , …”

Section: Introductionmentioning

confidence: 99%

“…By this approach, excellent results have been obtained in the design and selection of new drugs for different pharmacological fields 23−25 and more recently in crop protection. 26,27 The fungal cell wall is a preferred and safe target for fungicides. Most of the major cell wall components and enzymes that assemble them are not present in humans, other mammals, or plants.…”

Section: Introductionmentioning

confidence: 99%

Rational Design of Chitin Deacetylase Inhibitors for Sustainable Agricultural Use Based on Molecular Topology

Zanni

Martínez-Cruz

Gálvez-Llompart

et al. 2022

J. Agric. Food Chem.

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Fungicide resistance is a major concern in modern agriculture; therefore, there is a pressing demand to develop new, greener chemicals. Chitin is a major component of the fungal cell wall and a well-known elicitor of plant immunity. To overcome chitin recognition, fungal pathogens developed different strategies, with chitin deacetylase (CDA) activity being the most conserved. This enzyme is responsible for hydrolyzing the N-acetamido group in N-acetylglucosamine units of chitin to convert it to chitosan, a compound that can no longer be recognized by the plant. In previous works, we observed that treatments with CDA inhibitors, such as carboxylic acids, reduced the symptoms of cucurbit powdery mildew and induced rapid activation of chitin-triggered immunity, indicating that CDA could be an interesting target for fungicide development. In this work, we developed an in silico strategy based on QSAR (quantitative structure-activity relationship) and molecular topology (MT) to discover new, specific, and potent CAD inhibitors. Starting with the chemical structures of few carboxylic acids, with and without disease control activity, three predictive equations based on the MT paradigm were developed to identify a group of potential molecules. Their fungicidal activity was experimentally tested, and their specificity as CDA inhibitors was studied for the three best candidates by molecular docking simulations. To our knowledge, this is the first time that MT has been used for the identification of potential CDA inhibitors to be used against resistant powdery mildew strains. In this sense, we consider of special interest the discovery of molecules capable of stimulating the immune system of plants by triggering a defensive response against fungal species that are highly resistant to fungicides such as powdery mildew.

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Molecular topology and QSAR multi-target analysis to boost the in silico research for fungicides in agricultural chemistry

Cited by 7 publications

References 23 publications

Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

Application of SSIR Method for the Design of Fungicides

Rational Design of Chitin Deacetylase Inhibitors for Sustainable Agricultural Use Based on Molecular Topology

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