Antifungal

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.[3] 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

Azole antifungals inhibit conversion of lanosterol to ergosterol by inhibition of lanosterol 14α-demethylase.[4] 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.

• Bifonazole
• Butoconazole
• Clotrimazole
• Econazole
• Fenticonazole
• Isoconazole
• Ketoconazole
• Luliconazole
• Miconazole
• Omoconazole
• Oxiconazole
• Sertaconazole
• Sulconazole
• Tioconazole

• Albaconazole
• Efinaconazole
• Epoxiconazole
• Fluconazole
• Isavuconazole
• Itraconazole
• Posaconazole
• Propiconazole
• Ravuconazole
• Terconazole
• Voriconazole

• Abafungin

Allylamines[5] inhibit squalene epoxidase, another enzyme required for ergosterol synthesis. Examples include butenafine, naftifine, and terbinafine.[6][7][8]

Echinocandins inhibit the creation of glucan in the fungal cell wall by inhibiting 1,3-Beta-glucan synthase:

• Anidulafungin
• Caspofungin
• Micafungin

Echinocandins are administered intravenously, particularly for the treatment of resistant Candida species.[9][10]

• Ibrexafungerp

• Acrisorcin
• Amorolfine – a morpholine derivative used topically in dermatophytosis[11]
• Aurones – possess antifungal properties[12]
• Benzoic acid – has antifungal properties, such as in Whitfield's ointment, Friar's Balsam, and Balsam of Peru[13]
• 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.[14]
• Clioquinol
• Coal tar
• Copper(II) sulfate[15]
• Crystal violet – a triarylmethane dye. It has antibacterial, antifungal, and anthelmintic properties and was formerly important as a topical antiseptic.[16]
• Chlorophetanol
• Diiodohydroxyquinoline (Iodoquinol)
• Flucytosine (5-fluorocytosine) – an antimetabolite pyrimidine analog[17]
• Fumagillin
• Griseofulvin – binds to microtubules and inhibits mitosis[18]
• Haloprogin – discontinued due to the emergence of antifungals with fewer side effects[19]
• Miltefosine – disrupts fungal cell membrane dynamics by interacting with ergosterol[20]
• Nikkomycin – blocks formation of chitin present in the cell wall of fungus.
• Orotomide (F901318) – pyrimidine synthesis inhibitor[21][22]
• Piroctone olamine
• Pentanenitrile
• Potassium iodide – preferred treatment for lymphocutaneous sporotrichosis and subcutaneous zygomycosis (basidiobolomycosis). The mode of action is obscure.[23]
• 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[24]
• Undecylenic acid – an unsaturated fatty acid derived from natural castor oil; fungistatic, antibacterial, antiviral, and inhibits Candida morphogenesis
• Zinc pyrithione