Mechanism of Action - Antifungals - Exam 2

Question 1

Tolnaftate (tinactin)

Answer 1

Inhibits fungal squalene epoxidase, resulting in decreased ergosterol biosynthesis

Question 2

Azoles

Answer 2

inhibit CYP450, which catalyzes 14-alpha-demthylation of lanosterol during its conversion to egosterol

In the presence of azoles – iron is occupied – this inhibits the binding and activation of molecular oxygen by CYP450 and therefore inhibits the conversion of lanosterol to ergosterol

Question 3

Griseofulvin

Answer 3

isrupts the mitotic spindle by binding to polymerized microtubules to inhibit mitosis (recall that the dynamics of polymerization and depolymerization are linked to cell division)

Question 4

Amphotericin B

Answer 4

binds to ergosterol in the membranes of sensitive fungi – pores open in the membranes – allowing leakage of ions and small organic molecules

Question 5

5-Fluorocytosine

Answer 5

susceptible fungi convert 5-fluorocytosine to 5-fluorouracil, which is converted into 5-fluorodeoxyuridine monophosphage – 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase, thus inhibiting DNA biosynthesis

Question 6

Echinocandins

Answer 6

1,3-B-glucan synthesis in fungal cell wall by noncompetitive inhibition of 1,3-B-glucan synthase