Fungicide MOA

Chemical Class of Fungicide - Aliphatic nitrogens (Amines/guanidines) - Amides/anilides, including acylamino acids - Antibiotics - Aromatics Arsenicals - Aryl ketones Benzimidazoles - Benzothiazole Butanicals - Carbamates Azoles - Coppers Dicarboximides - Dinitrophenols Dithiocarbamates - Dithiolanes Mercury - Morpholines Organophosphorus - Organotin Oxazoles - Sulfurs Pyrazoles - Pyridines Pyrimidines - Pyrroles Quinolines - Quinones Thiazoles/thiadiazoles - 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

Steroid in biological systems Animal Insect Ecdysteroids such as ecdysterone Vertebrate Steroid hormones Sex steroids are a subset of sex hormones that produce sex differences or support reproduction. They include androgens, estrogens, and progestagens. Corticosteroids include glucocorticoids and mineralocorticoids. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids. Anabolic steroids are a class of steroids that interact with androgen receptors to increase muscle and bone synthesis. There are natural and synthetic anabolic steroids. In popular language, the word "steroids" usually refers to anabolic steroids. Cholesterol, which modulates the fluidity of cell membranes and is the principal constituent of the plaques implicated in atherosclerosis. Plant Phytosterols Brassinosteroids Fungus Ergosterols Source: Wikipedia

Ergosterol biosynthesis A Key steroid for fungal membrane In cell membrane, up to 40% biomass is steroid Mammalian steroid can be originated from ergosterol

Sterol biosynthesis in fungi, plant and animal

Steroid biosynthesis link

Sterol biosynthesis in mammalian

Sterol biosynthesis in fungi 1

Sterol biosynthesis in fungi 2

Numerous genes/proteins in Ergosterol biosynthesis

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

General structures of C14-demethylase inhibitor Azoles

Structures (continued)

MOA of Azole Fungicides Non-covalent complex formation with Fe in cytochrome P450

C14-Demethylase Remove 14-Methyl of lanosterol by consecutive addition of oxygen and decarboxylation CYP type protein: CYP55

Binding of Ligand to CYP

Steps, inhibited by EBIs

Azoles in medicine Ketoconazole Itraconazole Epidermophyton floccosum Microsporum audouinii Trichophyton spp. Ketoconazole Itraconazole

Problems in azole fungicides Cross-species reactivity! Uniconazole Paclobutrazole Myclobutanil