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Fungicide MOA
Chemical Class of Fungicide
-
Aliphatic nitrogens (Amines/guanidines)
Antibiotics
Arsenicals
Benzimidazoles
Butanicals
Azoles
Dicarboximides
Dithiocarbamates
Mercury
Organophosphorus
Oxazoles
Pyrazoles
Pyrimidines
Quinolines
Thiazoles/thiadiazoles
-
Amides/anilides, including acylamino acids
Aromatics
Aryl ketones
Benzothiazole
Carbamates
Coppers
Dinitrophenols
Dithiolanes
Morpholines
Organotin
Sulfurs
Pyridines
Pyrroles
Quinones
Miscellaneous
Biological class
•
•
•
•
•
•
•
•
•
•
•
Steroid biosynthesis
Mitosis/division
Respiration
Amino acid/protein biosynthesis
Lipid and membrane synthesis
Nucleic acid biosynthesis
Glucan biosynthesis
Melanin biosynthesis
Host-defense activation
Multi-site action
Unknown
MOA of Ergosterol Biosynthesis Inhibitor
•
•
•
•
•
•
•
•
•
Azoles: Triazole, Imidazole
Piperazines
Pyrimidines
Morpholines
Piperidines
Spiroketal amine
Hydroxyanilides
Allylamines
Thiocarbamates
MOA of Each Classes
• C14-Demethylase (erg11/cyp55)
• D14-reductase(erg24) and D8D7
isomerase (erg2)
• 3-Keto reductase in C4-demethylation
• Squalene epoxidase
Steps, inhibited by EBIs
Chemical Structures: D14-Reductase
Precursor
Product
Chemical structures of C4-Demethylase
Chemical Structures of Squalene epoxidase
inhibitor
Synthesis of Lanosterol from Squalene
Terbinafine (Lamisil)
Enzyme: Flavoprotein
In animal, squalene and its derivatives are key precursors of cholesterol
Mitosis inhibitors
Tubulin in cell organization
• Tubulin: a, b, g, d- etc….
• Major function:
– As a cytoskeleton
– Polar coordination of
chromosome
Benzimidazole fungicide
• Most of the benzimidazole (thiophanate,
benomyl) can be easily converted into
carbendazim-like structrure
• Inhibit the microfilament formation by
destabilization of b-tubulin
Inhibitors of Spectrin-like protein
delocalization
• Relatively novel inhibitors
• Spectrin: major role(s) is the maintenance
of cytoskeleton
• Interferene of spetrin results in
disintegration of cell organelles
Targets of Respiration Inhibitors
• Complex I (NADH oxidoreductase)
• Complex II (succinate dehydrogenase)
• Complex III (cytochrome bc1, complex,
Ubiquinol oxidase, Qo site )
• Complex III (ubiquinone reductase, Qi site)
• Uncoupler
• ATP synthase
Respiratory chain (electron transport chain)
Respiratory quinone
Chemical structures of complex I
inhibitor
Chem. Str. Of Complex II
Chem. Str. Of Complex III
Chem. Str. Of Complex III inhibitor
Uncouplers
ATP synthase inhibitor