Review of strobilurin fungicide chemicals

Balba, H. M.

doi:10.1080/03601230701316465

Cited by 335 publications

(225 citation statements)

References 17 publications

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“…The molecular targets of the HIF-1 inhibitors identified from our screen remain to be defined. A structure-based patent search revealed that the alkyliminophenylacetate compounds contain the toxophores of the strobilurin fungicides (32,33). Azoxystrobin inhibits electron transfer in the cytochrome bc1 complex of the mitochondrial respiratory chain before cytochrome b, resulting in the preventing cytochrome b reduction and thereby attenuating ROS production (35,36).…”

Section: Discussionmentioning

confidence: 99%

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Lin¹,

David

Donnelly

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

104

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Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development and progression by regulating genes that are vital for proliferation, glycolysis, angiogenesis, and metastasis. To identify strategies of targeting the HIF-1 pathway, we screened a siRNA library against the entire druggable genome and a small-molecule library consisting of 691,200 compounds using a HIF-1 reporter cell line. Although the siRNA library screen failed to reveal any druggable targets, the small-molecule library screen identified a class of alkyliminophenylacetate compounds that inhibit hypoxia-induced HIF-1 reporter activity at single-digit nanomolar concentrations. These compounds were found to inhibit hypoxia but not deferoxamine-induced HIF-1␣ protein stabilization. Further analysis indicated that the alkyliminophenylacetate compounds likely inhibit the HIF-1 pathway through blocking the hypoxia-induced mitochondrial reactive oxygen species (ROS) production. Strikingly, all of the nonalkyliminophenylacetate HIF-1 inhibitors identified from the small-molecule library screen were also found to target mitochondria like the alkyliminophenylacetate compounds. The exclusive enrichment of mitochondria inhibitors from a library of >600,000 diverse compounds by using the HIF-1 reporter assay highlights the essential role of mitochondria in HIF-1 regulation. These results also suggest that targeting mitochondrial ROS production might be a highly effective way of blocking HIF-1 activity in tumors.hypoxia-inducible factor ͉ hypoxia ͉ reactive oxygen species ͉ siRNA ͉ RNAi H ypoxia-inducible factor-1 (HIF-1) is the master regulator of cellular responses to low oxygen (1-3). It consists of a constitutively expressed ␤ subunit and an oxygen-regulated ␣ subunit. The proline hydroxylase domain-containing proteins (PHDs) were originally thought to be the main oxygen sensor that mediates oxygen-dependent HIF-1␣ degradation. Under aerobic conditions, PHDs hydroxylate HIF-1␣ at key proline residues by using oxygen as a substrate, which ultimately causes polyubiquitination and degradation of HIF-1␣ through an E3 ubiquitin ligase complex containing the von Hippel-Lindau protein (4, 5). Because oxygen is required for PHD-mediated hydroxylation, the low oxygen level under hypoxic conditions prevents HIF-1␣ hydroxylation, which subsequently leads to the stabilization of HIF-1␣. However, several recent studies demonstrate that the hypoxia-induced production of reactive oxygen species (ROS) in mitochondria is both necessary and sufficient for hypoxia-dependent HIF-1␣ accumulation, suggesting that mitochondria may act as an oxygen sensor for HIF-1␣ regulation by generating ROS under hypoxic conditions (6-9).HIF-1 has emerged as an attractive target for cancer therapy in the last several years. The requirement of HIF-1 for tumor growth has been examined by abrogating the HIF-1 pathway in tumors by using RNAi, small molecule inhibitors, or genetic alterations. Although the degree of tumor responses to HIF-1 inhibition varies among studies, the major...

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Section: Discussionmentioning

confidence: 99%

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Lin¹,

David

Donnelly

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

104

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“…They have played a role in the disease management of various agricultural products and are widely used, accounting for over 10% of the fungicide market (Bartlett et al, 2002). The mode of action in fungi is to bind to the quinol oxidation site of cytochrome b in the mitochondrial electron transport chain and thereby block electron transfer, which leads to the inhibition of energy (ATP) production and then the fungi ultimately die (Balba, 2007). Among the strobilurin class, trifloxystrobin (TRF) is a broad-spectrum, widely-used fungicide.…”

Section: Introductionmentioning

confidence: 99%

Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes

et al. 2016

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-Trifloxystrobin is a strobilurin class fungicide, the mode of action of which is to block the mitochondrial electron transport chain and inhibit energy production in fungi. Although adverse effects have been reported by occupational or environmental exposure of fungicides, the pathophysiological mechanism in human cells remains poorly understood. In the present study, we investigated the impact of trifloxystrobin on exposed skin at the cellular organelle level using HaCaT, the human skin keratinocyte cell line. Cells were treated with trifloxystrobin for 48 hr and trifloxystrobin showed detrimental effects on mitochondria evidenced by altered mitochondrial membrane potential and morphology. To identify autophagic degradation of the damaged mitochondria, confocal imaging and Western blotting were performed. Trifloxystrobin induced autophagy-related proteins in HaCaT cells. The mitochondrial reactive oxygen species scavenger mitoTEMPO was applied to further explore the mechanism of trifloxystrobinmediated mitophagy in human skin cells. PINK1 and Parkin were overexpressed by trifloxystrobin, and mitoTEMPO alleviated the effects on mitophagy induction. Taken together, our findings indicated that mitochondrial damage and mitophagy may play a role in trifloxystrobin-induced toxicity in human keratinocytes and this could be suggested as a mechanism of cutaneous diseases developed by exposure.

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“…In this context, a long term experiment was conducted to evaluate the efficacy of new generation bio-rational fungicide of 'strobilurin derivatives' . Strobilurins (also known as β-methoxyacrylates) or QoI (Quinone outside Inhibitors) fungicides, launched in 1996 are analogues of strobilurin-A [4] originally derived from natural products [5] (Strobilurus tenacellus, a wild mushroom growing in forests). Strobilurins, are now the second largest chemistry group of fungicides, widely used on cereals and, more recently, on soybeans (a market that reached $600 million in 2004).…”

Section: Introductionmentioning

confidence: 99%

Bioefficacy of Strobilurin Based Fungicides against Rice Sheath Blight Disease

Mk¹,

Yadav²,

Ak³

2016

Transcriptomics

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As the usage of fungicides catapulted with the onward march of the dial hour, fungicidal resistance by the pathogens emerged as a new constraint. This amalgamated with the growing demand by the farmers for crop protection agents with low use rates, a benign environmental profile and a low toxicity to human and wild life, further gave an impetus to the search of new molecule of fungicides with novel modes of action. Sheath blight of rice caused by Rhizoctonia solani Kühn is one of the devastating diseases in eastern part of India. Various attempts were taken to develop sheath blight resistant variety but till date no such varieties were released. Various cultural practices combined with use of fungicides are the most common option of managing the disease. Repeated use of same fungicides in the same field sometimes become less or not effective, may be due to development of resistance recombinant of R. solani. Several experiment proved strobilurin based molecules like azoxystrobin, trifloxystrobin, metominostrobin manage the disease effectively and eco-friendly way than other commercially available fungicides.

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Review of strobilurin fungicide chemicals

Cited by 335 publications

References 17 publications

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes

Bioefficacy of Strobilurin Based Fungicides against Rice Sheath Blight Disease

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