1. Fungicide MOA

2. 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

3. 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

4. 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

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

6. Sterol biosynthesis in fungi, plant and animal

7. Steroid biosynthesis link

8. Sterol biosynthesis in mammalian

9. Sterol biosynthesis in fungi 1

10. Sterol biosynthesis in fungi 2

11. Numerous genes/proteins in Ergosterol biosynthesis

12. MOA of Ergosterol Biosynthesis Inhibitor
Azoles: Triazole, Imidazole
Piperazines
Pyrimidines
Morpholines
Piperidines
Spiroketal amine
Hydroxyanilides
Allylamines
Thiocarbamates

13. MOA of Each Classes C14-Demethylase (erg11/cyp55)
D14-reductase(erg24) and D8D7 isomerase (erg2)
3-Keto reductase in C4-demethylation
Squalene epoxidase

14. General structures of C14-demethylase inhibitor
Azoles

15. Structures (continued)

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

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

18. Binding of Ligand to CYP

19. Steps, inhibited by EBIs

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

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