Polyene Antifungals

Polyene antifungals are characterized by having a large macrolide ring of carbon atoms closed by
the formation of an internal ester or lactone. These polyene antimycotics are typically obtained
from some species of Streptomyces bacteria. The polyenes bind to ergosterol in the fungal cell
membrane and thus weakens it, causing leakage of K+ and Na+ ions, which may contribute to
fungal cell death.
Examples: Ampothericin B, Nystatin, Natamycin

Azole antifungals
The azole derivatives are classified as imidazoles or triazoles on the basis of whether they have
two or three nitrogen atoms in the five- membered azole ring. Many azoles work by inhibiting the
fungal enzyme 14-demethylase which produces ergosterol (an important component of the
fungal plasma membrane).
Examples: clotrimazole, miconazole, econazole and ketoconazole are currently in clinical use;
newer drugs such as itraconazole, fluconazole and voriconazole have important applications in
the treatment of systemic infections

Echinocandins
The echinocandins are a relatively new group of antifungal drug and are semisynthetic
lipopeptides comprising a cyclic hexapeptide core connected to a lateral fatty acid chain. They
inhibit the synthesis of glucan in the cell wall, via noncompetitive inhibition of the enzyme 1,3-
glucan synthase
Examples: caspofungin, micafungin and anidulafungin

Synthetic antifungal agents

Flucytosine is a synthetic fluorinated pyrimidine which has been used as an oral antifungal agent
and demonstrates good activity against a range of yeast species and moderate levels of activity
against Aspergillus species. Two major mechanisms of action have been elucidated:
Flucytosine is intrafungally converted into the cytostatic fluorouracil which undergoes further
steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis thus
disturbing the building of certain essential proteins.
Flucytosine also undergoes conversion into 5-fluorodeoxyuridinemonophosphate which inhibits
fungal DNA synthesis.
Example: Flucytosine