mepronil
{{Chembox
| ImageFile = Mepronil.svg
| ImageSize =
| ImageAlt =
| IUPACName = 2-methyl-N-(3-propan-2-yloxyphenyl)benzamide
| OtherNames = KCO-1
| Section1 = {{Chembox Identifiers
| CASNo = 55814-41-0
| CASNo_Ref = {{cascite|correct|CAS}}
|EINECS = 611-317-4
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = QJK1MXY8DW
| ChEBI = 81823
| ChEMBL = 1615095
| SMILES = CC1=CC=CC=C1C(=O)NC2=CC(=CC=C2)OC(C)C
| PubChem = 41632
| ChemSpiderID = 37994
| StdInChI = 1S/C17H19NO2/c1-12(2)20-15-9-6-8-14(11-15)18-17(19)16-10-5-4-7-13(16)3/h4-12H,1-3H3,(H,18,19)
| StdInChIKey = BCTQJXQXJVLSIG-UHFFFAOYSA-N
}}
| Section2 = {{Chembox Properties
| C=17 | H=19 | N=1 | O=2
| Appearance = Off-white powder
| Odor =
| Density = 1.11 g/cm3
| MeltingPtC = 91.4
| MeltingPt_ref =
| BoilingPt =
|LogP = 3.66
| Solubility = Slightly soluble (12.1 mg/L, 20 °C)
| SolubleOther =
| Solvent =
}}
| Section3 = {{Chembox Hazards
| Hazards_ref={{cite web |url=https://pubchem.ncbi.nlm.nih.gov/compound/41632 |title=Mepronil |access-date=2024-05-04}}
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
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Mepronil is a fungicide used as a seed treatment or foliar spray in agriculture to protect crops from fungal diseases. It was first marketed by Kumiai Chemical Industries in 1981 using their brand name Basitac.{{cite web |url=http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/438.htm |title=Mepronil |publisher=University of Hertfordshire |author=Pesticide Properties Database }} The compound is a benzanilide which combines 2-methylbenzoic acid with the O-isopropyl derivative of 3-aminophenol to give an inhibitor of succinate dehydrogenase (SDHI).{{Cite book |isbn=0948404019 | title = The Pesticide Manual - A World Compendium | edition = Eighth | editor = Worthing C.R. | publisher = British Crop Protection Council | date = 1987 |page=489 }}{{cite book |doi=10.1002/9783527693931.ch31 |chapter=Fungicidal Succinate-Dehydrogenase-Inhibiting Carboxamides |title=Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals |year=2016 |last1=Walter |first1=Harald |editor-last1=Lamberth |editor-first1=Clemens |editor-first2=Jürgen |editor-last2= Dinges |publisher=Wiley |pages=405–425 |isbn=9783527339471 }}
History
Inhibition of succinate dehydrogenase, the complex II in the mitochondrial respiration chain, has been known as a fungicidal mechanism of action since the first examples were marketed in the 1960s. The first compound in this class was carboxin, which had a narrow spectrum of useful biological activity, mainly on basidiomycetes and was used as a seed treatment.{{cite web |url=https://www.frac.info/frac-teams/working-groups/sdhi-fungicides/information |title=History of SDHI-fungicides |website=frac.info |access-date=2024-05-04 }} Many further examples of this mechanism of action were developed by crop protection companies seeking compounds with improved properties and mepronil was developed owing to its effectiveness as a foliar application and by seed treatment.{{cite journal |doi=10.1584/jpestics.10.315 |title=Development of a New Fungicide, Mepronil |date=1985 |last1=Kawada |first1=Seigo |last2=Sakamoto |first2=Akira |last3=Shimazaki |first3=Isao |journal=Journal of Pesticide Science |volume=10 |issue=2 |pages=315–324 }}
Synthesis
Mepronil combines the acid chloride of 2-methylbenzoic acid with an aniline derivative which was made from 3-aminophenol.{{cite patent |country=US |number=3937840 |status=patent |title=Compositions and methods of combatting bacteria and fungi using 2-methylbenzanilide derivatives |pubdate=1976-02-10 |fdate=1974-07-17 |pridate=1975-08-15 |invent1=Chiyomaru, I |invent2=Kawada, S |invent3= Takita, K |assign1=Kumiai Chemical Industry Co Ltd }}{{cite book |isbn=0815514018 |url=https://books.google.com/books?id=-9cHDi8OOO4C&pg=PA33 | title=Pesticide Synthesis Handbook | last1=Unger | first1=Thomas A. | date=31 December 1996 | publisher=William Andrew |page=33 }}
Mechanism of action
SDHI of this type act by binding at the quinone reduction site of the enzyme complex, preventing ubiquinone from doing so. As a consequence, the tricarboxylic acid cycle and electron transport chain cannot function.{{cite journal |doi=10.1074/jbc.M311876200 |doi-access=free |title=The Quaternary Structure of the Saccharomyces cerevisiae Succinate Dehydrogenase |year=2004 |last1=Oyedotun |first1=Kayode S. |last2=Lemire |first2=Bernard D. |journal=Journal of Biological Chemistry |volume=279 |issue=10 |pages=9424–9431 |pmid=14672929 }}{{cite journal |doi=10.1016/j.cropro.2010.02.019 |title=Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi |year=2010 |last1=Avenot |first1=Hervé F. |last2=Michailides |first2=Themis J. |journal=Crop Protection |volume=29 |issue=7 |pages=643–651 }}
Usage
Mepronil has been used since 1981 as a seed treatment to control Rhizoctonia solani on vegetables. It is also used by foliar application to control R. solani on rice, Gymnosporangium fuscum (rust) on pears and Puccinia chrysanthemi on chrysanthemums. As of 2024 it is no longer registered for use, having been superseded by alternative SDHI products.
Resistance management
Fungal populations have the ability to develop resistance to SDHI inhibitors. This potential can be mitigated by careful management. Reports of individual pest species becoming resistant are monitored by manufacturers, regulatory bodies such as the EPA and the Fungicides Resistance Action Committee (FRAC).{{cite web |url=https://www.frac.info/ |title=Fungicides Resistance Action Committee website}} The risks of resistance developing can be reduced by using a mixture of two or more fungicides which each have activity on relevant pests but with unrelated mechanisms of action. FRAC assigns fungicides into classes so as to facilitate this.
Brands
Mepronil is the ISO common name{{cite web |url=http://www.bcpcpesticidecompendium.org/mepronil.html |title=Compendium of Pesticide Common Names: Mepronil |publisher=BCPC |access-date=2024-05-04}} for the active ingredient which is formulated into the branded product sold to end-users. Basitac was the brand name used for Kumiai's products.