Innovative selection approach for a new antifungal agent mefentrifluconazole (Revysol®) and the impact upon its toxicity profile

Tesh, S. A.; Tesh, J.M.; Fegert, Ivana; Buesen, Roland; Schneider, Steffen; Mentzel, Tobias; Ravenzwaay, Bennard van; Stinchcombe, Stefan

doi:10.1016/j.yrtph.2019.04.009

Cited by 46 publications

(25 citation statements)

References 32 publications

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“…Despite intensive use and in contrast to other systemic and target-site fungicides, the azoles are still contributing positively to a wide range of disease control, as can be seen, for example, in winter wheat ( Jørgensen et al., 2021a ). This constant benefit has been driven by the development of more potent azoles over the years ( Russell, 2005 ; Parker et al., 2011 ; Tesh et al., 2019 ) and the moderate risk of resistance development ( ). In practice, azole compounds have been widely used either as solo products or in a mixture with other active ingredients to broaden the control spectrum or minimize the risk of resistance development.…”

Section: Azole Use In a Greater Contextmentioning

confidence: 99%

“…It has been shown that azole fungicides differ widely in their potency to inhibit the human aromatase enzyme ( Trösken et al., 2004 ). Consequently, the screening strategy for new azole fungicides aims to identify candidates with a high fungicidal activity and minimal likelihood of adverse side effects that would indicate an endocrine-disrupting potential ( Tesh et al., 2019 ).…”

Section: Azole Use In a Greater Contextmentioning

confidence: 99%

“…Microbiological methods, screening for MIC 50 values, molecular biological studies, and protein modeling, are expected to support future azole development to achieve a better specificity for the target enzymes and minimize the risk of cross-resistance ( Parker et al., 2014 ). The skill of designing new molecules, which minimize the risk of undesirable effects, is ongoing, as described for mefentrifluconazole in a recent paper ( Tesh et al., 2019 ).…”

Section: Azole Use In a Greater Contextmentioning

confidence: 99%

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Azole Use in Agriculture, Horticulture, and Wood Preservation – Is It Indispensable?

Jørgensen

Heick

2021

Front. Cell. Infect. Microbiol.

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Plant pathogens cause significant damage to plant products, compromising both quantities and quality. Even though many elements of agricultural practices are an integral part of reducing disease attacks, modern agriculture is still highly reliant on fungicides to guarantee high yields and product quality. The azoles, 14-alpha demethylase inhibitors, have been the fungicide class used most widely to control fungal plant diseases for more than four decades. More than 25 different azoles have been developed for the control of plant diseases in crops and the group has a world market value share of 20-25%. Azoles have proven to provide long-lasting control of many target plant pathogens and are categorized to have moderate risk for developing fungicide resistance. Field performances against many fungal pathogens have correspondingly been stable or only moderately reduced over time. Hence azoles are still, to date, considered the backbone in many control strategies and widely used as solo fungicides or as mixing partners with other fungicide groups, broadening the control spectrum as well as minimizing the overall risk of resistance development. This review describes the historic perspective of azoles, their market shares and importance for production of major crops like cereals, rice, oilseed rape, sugar beet, banana, citrus, and soybeans. In addition, information regarding use in amenity grass, in the wood preservation industry and as plant growth regulators are described. At the end of the review azoles are discussed in a wider context including future threats following stricter requirements for registration and potential impact on human health.

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Section: Azole Use In a Greater Contextmentioning

confidence: 99%

Section: Azole Use In a Greater Contextmentioning

confidence: 99%

Section: Azole Use In a Greater Contextmentioning

confidence: 99%

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Azole Use in Agriculture, Horticulture, and Wood Preservation – Is It Indispensable?

Jørgensen

Heick

2021

Front. Cell. Infect. Microbiol.

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“…The novel fungicide ipflufenoquin potentially possessing a new mode of action has been registered for pear scab recently in Japan. Additionally, the new DMI fungicide mefentrifluconazole [ 74 ], effective against scab with a reportedly more favorable toxicity profile [ 75 ], is now under development. Use of these fungicides in combination with disease-resistance inducers [ 76 ] and/or newly released scab-resistant pear cultivars [ 4 , 7 ] will be useful for integrated scab control in future.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

DMI-Fungicide Resistance in Venturia nashicola, the Causal Agent of Asian Pear Scab—How Reliable Are Mycelial Growth Tests in Culture?

et al. 2021

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Scab, caused by Venturia nashicola, is among the most serious diseases of Asian pears and control of this disease largely relies on sterol demethylation inhibitor (DMI) fungicides. However, pear growers have complained about field performance of DMIs since the mid-2000s. In this study, to evaluate pathogen sensitivity, mycelial growth tests and inoculation tests were conducted using DMI-amended culture medium and fungicide-sprayed potted pear trees, respectively. Results confirmed distribution of isolates resistant to fenarimol, hexaconazole, and difenoconazole in the field populations. Importantly, results from tests in culture did not fully correlate with those from tests in planta. Due to phenotypic instability of resistance and poor sporulation of this pathogen in culture, resistance is generally assessed by laborious and time-consuming inoculation with conidia collected from a field. To improve the result interpretation from in vitro tests, the isolates were genotyped: the CYP51 gene which encodes the target sterol 14α-demethylase was sequenced and various mutations have been detected in the coding sequence of DMI-resistant isolates. In addition to the detected single nucleotide polymorphisms, alternative mechanisms, not based on changes in the structure of the target protein, may also increase DMI resistance. Development of molecular methods for the diagnosis of DMI resistance seems to be challenging in V. nashicola.

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“…Mefentrifluconazole (MFZ), [(2RS)‐2‐[4‐(4‐chlorophenoxy)‐α,α,α‐trifluoro‐o‐tolyl]‐1‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ol], is a new type of isopropanol‐triazole fungicide 11,12 . Unlike traditional triazole fungicides, MFZ has unique isopropanol moiety molecular structure, which is more conducive to binding to the target protein and has limited cross‐resistance and higher efficacy 13,14 . Since 2016, MFZ has been registered in France, New Zealand, Colombia, Australia, Korea, Canada, the United Kingdom, the United States, and China for the prevention and treatment of diseases in many crops, including field crops (such as corn, grains, soybeans, and rice), economic crops (such as green peppers and grapes), lawns and ornamental plants.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio)

Ren

Zhao

et al. 2022

Environmental Toxicology

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The research on the enantioselective toxic effects of chiral pesticides on non‐target aquatic organisms has attracted more and more attention. This study investigated the enantioselective toxic effects of mefentrifluconazole (MFZ) on acute toxicity, developmental toxicity, locomotor behaviors, and the mRNA relative expression levels of genes related to neurodevelopment and cardiac development in zebrafish embryos or larvae. The 96‐h lethal concentration 50 (LC50) values (exposed to racemate and enantiomers of MFZ, that is, rac‐MFZ/(−)‐MFZ/(+)‐MFZ) were 1.010, 1.552, and 0.753 mg/L for embryo, and 0.753, 1.187, and 0.553 mg/L for larvae. The rac‐MFZ/(−)‐MFZ/(+)‐MFZ can affect the heart development of zebrafish embryos, accompanied by heart rate inhibition, yolk sac deformities, pericardial deformities, and down‐regulation of genes related to cardiotoxicity in larvae in an enantioselective manner. Moreover, the rac‐MFZ/(−)‐MFZ/(+)‐MFZ also can affect the neural development of zebrafish embryos, accompanied by autonomic movement inhibition, swimming speed and swimming distance abnormalities, and down‐regulation of genes related to neurotoxicity in larvae in an enantioselective manner. For all toxicity endpoints, the effect of the (+)‐MFZ to early‐staged zebrafish were significantly greater than that of (−)‐MFZ. These results will help distinguishing the difference of MFZ enantiomers to zebrafish, and provide scientific reference for improving the risk assessment of chiral pesticides MFZ.

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Innovative selection approach for a new antifungal agent mefentrifluconazole (Revysol®) and the impact upon its toxicity profile

Cited by 46 publications

References 32 publications

Azole Use in Agriculture, Horticulture, and Wood Preservation – Is It Indispensable?

Azole Use in Agriculture, Horticulture, and Wood Preservation – Is It Indispensable?

DMI-Fungicide Resistance in Venturia nashicola, the Causal Agent of Asian Pear Scab—How Reliable Are Mycelial Growth Tests in Culture?

Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio)

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