Discovery of N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides as potential succinate dehydrogenase inhibitors

Design, Synthesis, and Antifungal Activity of Novel Thiophene/Furan-1,3,4-Oxadiazole Carboxamides as Potent Succinate Dehydrogenase Inhibitors

“…DCPIP reduction was kept at 30 °C and detected at 595 nm. Finally, calculated absorbance slopes (OD/ h) were utilized to calculate IC 50 using a data processing system (SPSS statistics 25).…”

“…These SDHIs have a similar heterocyclic acid scaffold, such as pyrazole and pyridine rings. In recent years, a majority of studies have concentrated on the modification of the amine group with retaining the core moieties of commercial SDHIs, which may lead to structural similarity and cross-resistance more easily. − Consequently, the research on structure modification and optimization of a novel carboxyl acid core moiety could be another important direction for the development of novel SDHIs.…”

Expedient Discovery for Novel Antifungal Leads Targeting Succinate Dehydrogenase: Pyrazole-4-formylhydrazide Derivatives Bearing a Diphenyl Ether Fragment

“…The in vitro antifungal effects of title compounds against the above phytopathogenic fungi were evaluated using a mycelium growth rate method that is briefly described as follows: ,,− ,− 100 μL dimethylsulfoxide (DMSO) dissolved in a tested compound was added into 45 mL of potato dextrose agar (PDA). After shaking well, the obtained mixture was equally divided and poured into three nine-centimeter Petri plates.…”

“…The electron transfers along mitochondrial respiratory enzyme complexes generate a vital proton gradient across the cellular membrane, which activates adenosine 5′-triphosphate (ATP) synthase that translates adenosine 5′-diphosphate into ATP. , The above oxidative phosphorylation on cellular mitochondria produces essential energies for maintaining normal physiological and biochemical reactions within aerobic eukaryotes. , In this pivotal biochemical process, succinate dehydrogenase (SDH), recognized as the crucial component of respiratory enzyme complexes, catalyzes succinate oxidation coupling with electron transfers from succinate to ubiquinone. − Over the past half a century, practical explorations have confirmed that inhibiting the normal physiological function of SDH within phytopathogenic fungi could be an important strategy to effectively control the fungal infections in grains, vegetables, and fruits. − During the development process of succinate dehydrogenase inhibitors (SDHIs) that structurally possess a common carboxamide framework, a stable pyrazole-4-carboxamide fragment has emerged as the indispensable dominant scaffold (Figure ) that leads to a significant improvement in the antifungal effects of constructed carboxamides against phytopathogens. ,− Currently, introducing a flexible amide chain into pyrazole-4-carboxamide templates (e.g., isoflucypram, pyrapropoyne, and pydiflumetofen) is considered as an innovative exploitation strategy for SDHI structural optimization, which implicitly indicates the optimization importance of amide chain fragments for developing novel carboxamide fungicides with higher efficacies and broader biological spectra. − …”

Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

“…Currently, nearly 30 different products are sold on the French market alone that contain bixafen as sole active substance or mixed with other fungicides. Bixafen belongs to the succinate dehydrogenase inhibitor (SDHI) family, the fungicides most widely used in agriculture to fight a broad range of fungal diseases (Lal eve et al, 2014;Zhang et al, 2019). Bixafen, which is derived from carboxin and categorized as a latest-generation SDHIs, acts through inhibition of mitochondrial respiration chain complex II, also known as succinate dehydrogenase (SDH).…”