The available classes of antifungal drugs are still limited but as of 2021 novel classes of antifungals are being developed and are undergoing various stages of clinical trials to assess performance.
Polyenes A
polyene is a molecule with multiple
conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals
amphiphilic. The
polyene antimycotics bind with
sterols in the fungal
cell membrane, principally
ergosterol. This changes the transition temperature (Tg) of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. (In ordinary circumstances membrane sterols increase the packing of the phospholipid bilayer making the plasma membrane more dense.) As a result, the cell's contents including monovalent ions (K+, Na+, H+, and Cl−) and small organic molecules leak, which is regarded as one of the primary ways a cell dies. Animal cells contain
cholesterol instead of ergosterol and so they are much less susceptible. However, at therapeutic doses, some amphotericin B may bind to animal membrane cholesterol, increasing the risk of human toxicity. Amphotericin B is
nephrotoxic when given
intravenously. As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased. Therefore, further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals. •
Amphotericin B •
Candicidin •
Filipin – 35 carbons, binds to cholesterol (toxic) •
Hamycin •
Natamycin – 33 carbons, binds well to ergosterol •
Nystatin •
Rimocidin Azoles Azole antifungals inhibit the conversion of
lanosterol to
ergosterol by inhibiting
lanosterol 14α-demethylase. These compounds have a five-membered ring containing two or three nitrogen atoms. The imidazole antifungals contain a 1,3-diazole (
imidazole) ring (two nitrogen atoms), whereas the triazole antifungals have a ring with three nitrogen atoms. inhibit
squalene epoxidase, another enzyme required for
ergosterol synthesis. Examples include
butenafine,
naftifine, and
terbinafine.
Echinocandins Echinocandins inhibit the creation of
glucan in the fungal
cell wall by
inhibiting 1,3-Beta-glucan synthase: •
Anidulafungin •
Caspofungin •
Micafungin •
Rezafungin Echinocandins are administered intravenously, particularly for the treatment of resistant
Candida species.
Triterpenoids •
Ibrexafungerp Others •
Acrisorcin •
Amorolfine – a morpholine derivative used topically in dermatophytosis •
Aurones – possess antifungal properties •
Benzoic acid – has antifungal properties, such as in
Whitfield's ointment,
Friar's Balsam, and
Balsam of Peru •
Carbol fuchsin (Castellani's paint) •
Ciclopirox (ciclopirox olamine) – a hydroxypyridone antifungal that interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against
tinea versicolour. •
Clioquinol •
Coal tar •
Copper(II) sulfate •
Crystal violet – a
triarylmethane dye. It has antibacterial, antifungal, and
anthelmintic properties and was formerly important as a
topical antiseptic. •
Chlorhexidine is a topical antibacterial and antifungal. It is commonly used in hospitals as an antiseptic. It is much more strongly antibacterial than antifungal, requiring at least a 10 times higher concentration to kill yeast compared to gram negative bacteria •
Chlorophetanol •
Diiodohydroxyquinoline (Iodoquinol) •
Flucytosine (5-fluorocytosine) – an
antimetabolite pyrimidine analog •
Fumagillin •
Griseofulvin – binds to
microtubules and inhibits
mitosis •
Haloprogin – discontinued due to the emergence of antifungals with fewer side effects •
Miltefosine works by damaging fungal cell membranes •
Nikkomycin – blocks formation of chitin present in the cell wall of fungus. •
Orotomide (F901318) – pyrimidine synthesis inhibitor •
Piroctone olamine •
Pentanenitrile •
Potassium iodide – preferred treatment for lymphocutaneous
sporotrichosis and subcutaneous
zygomycosis (
basidiobolomycosis). The mode of action is obscure. •
Potassium permanganate - for use only on thicker, more insensitive skin such as the soles of the feet. •
Selenium disulfide •
Sodium thiosulfate •
Sulfur •
Tolnaftate – a thiocarbamate antifungal, which inhibits fungal squalene epoxidase (similar mechanism to allylamines like terbinafine) •
Triacetin – hydrolysed to acetic acid by fungal
esterases •
Undecylenic acid – an
unsaturated fatty acid derived from natural
castor oil; fungistatic, antibacterial, antiviral, and inhibits
Candida morphogenesis •
Zinc pyrithione ==Side effects==