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 D8D7 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
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