[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Antifungal therapy: fungal biology and drug targets # Antifungal therapy: fungal biology and drug targets Fungi are cells much like ours, so antifungals aim at the few parts that differ: the membrane sterol ergosterol and the cell wall. Updated Nov 12, 2026 On this page - The basics Key points - The membrane: ergosterol and its pathway - The cell wall - Nucleic acids and other targets - Spectrum and resistance - Toxicity follows the target - Memory aid - Example drugs - Clinical Why antifungals are hard to design - Study Test yourself - Connections Connections Fungi are eukaryotes, so most of their machinery resembles human cells, which makes selective drugs hard to find. Antifungals exploit three main differences: fungi use ergosterol instead of cholesterol in their membrane, they have a rigid cell wall made of glucan and chitin, and some can convert cytosine into fluorouracil. Each class hits one of these, and the target explains both its spectrum and its toxicity. ## Key points - Polyenes (amphotericin B, nystatin) bind ergosterol and open pores in the fungal membrane; some binding to human cholesterol explains kidney toxicity. - Azoles block lanosterol 14-alpha-demethylase (a fungal CYP enzyme), stopping ergosterol synthesis; they also inhibit human CYP enzymes, so interactions are common. - Echinocandins block beta-1,3-D-glucan synthesis in the cell wall, a structure human cells do not have. - Flucytosine is turned into fluorouracil only inside fungi, which have cytosine deaminase; it is combined with other drugs because resistance appears quickly. - Allylamines (terbinafine) inhibit squalene epoxidase, an earlier step of ergosterol synthesis; they are mainly used for skin and nail infections. ## Why antifungals are hard to design Bacteria are prokaryotes, with ribosomes and cell walls very unlike ours. Fungi share our type of ribosome, nucleus and many enzymes. Only a few targets are both essential for the fungus and absent or different in human cells. This explains why there are few antifungal classes, why several are toxic, and why invasive fungal infections still carry high mortality, especially in people with neutropenia, transplants, HIV or intensive care stays. ## The membrane: ergosterol and its pathway - Polyenes: amphotericin B binds membrane sterols, makes the membrane leaky and is fungicidal; it has a very broad spectrum. Lipid formulations reduce, but do not remove, kidney toxicity. - Azoles: imidazoles (clotrimazole, miconazole, ketoconazole) and triazoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole) inhibit 14-alpha-demethylase; toxic sterol intermediates build up and ergosterol runs out. - Allylamines: terbinafine blocks squalene epoxidase earlier in the same pathway and concentrates in skin and nails. ## The cell wall The fungal wall is a mesh of glucans, chitin and mannoproteins that keeps the cell from bursting. Echinocandins (caspofungin, micafungin, rezafungin) inhibit the glucan synthase complex, so the wall weakens. Human cells have no such wall, which is why echinocandins are among the best-tolerated antifungals. They are active against Candida and Aspergillus but not Cryptococcus. Ibrexafungerp is an oral drug that also inhibits glucan synthase. ## Nucleic acids and other targets Flucytosine enters fungal cells through a cytosine permease and is deaminated to fluorouracil, which disrupts RNA and DNA synthesis. Human cells lack cytosine deaminase, which gives selectivity. Used alone it quickly selects resistance, so it is combined, classically with amphotericin B for cryptococcal meningitis. Griseofulvin disrupts fungal microtubules and is used for some dermatophyte infections. ## Spectrum and resistance - Candida krusei is intrinsically resistant to fluconazole, and many C. glabrata isolates have reduced susceptibility. - Azole resistance arises from changes in the target gene (ERG11), overproduction of the target, or efflux pumps that push azoles out. - Echinocandin resistance comes from mutations in the glucan synthase subunits (FKS genes). - Candida auris is often multidrug resistant and spreads in hospitals. - Amphotericin B covers the endemic mycoses that matter in Latin America, such as histoplasmosis and paracoccidioidomycosis; itraconazole is used for milder forms and maintenance. ## Toxicity follows the target - Amphotericin B: infusion reactions (fever, chills), kidney injury, low potassium; its label warns to verify the product name and dose before each infusion, because formulations differ. - Azoles: liver injury, QT prolongation and many drug interactions through CYP3A4, CYP2C9 and CYP2C19 inhibition (warfarin, tacrolimus, some statins); avoided in pregnancy unless the infection is severe. - Echinocandins: few adverse effects; mainly infusion reactions and liver-test changes. - Flucytosine: bone marrow suppression, especially when kidney function is poor. ## Memory aid Membrane, Wall, Nucleus: polyenes and azoles hit the Membrane, echinocandins the Wall, flucytosine the Nucleic acids. ## Test yourself Think of the answer, then tap the question to see it. ## Why do echinocandins cause few adverse effects in humans? They inhibit beta-1,3-D-glucan synthesis in the fungal cell wall, and human cells have no cell wall. ## Why are drug interactions so common with azole antifungals? Azoles inhibit a fungal CYP enzyme but also human CYP enzymes such as CYP3A4, CYP2C9 and CYP2C19, raising levels of many other drugs. ## What makes flucytosine selective for fungi, and why is it combined with other drugs? Fungi have cytosine deaminase, which turns it into fluorouracil; human cells do not. Alone it rapidly selects resistance. ## Which Candida species is intrinsically resistant to fluconazole? Candida krusei. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/antifungal-therapy-fungal-biology-and-drug-targets/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Amphotericin B](https://durgical.com/en/pharmacology/amphotericin-b/) - [Nystatin](https://durgical.com/en/pharmacology/nystatin/) - [Fluconazole](https://durgical.com/en/pharmacology/fluconazole/) - [Itraconazole](https://durgical.com/en/pharmacology/itraconazole/) - [Voriconazole](https://durgical.com/en/pharmacology/voriconazole/) - [Posaconazole](https://durgical.com/en/pharmacology/posaconazole/) - [Isavuconazole](https://durgical.com/en/pharmacology/isavuconazole/) - [Caspofungin](https://durgical.com/en/pharmacology/caspofungin/) - [Micafungin](https://durgical.com/en/pharmacology/micafungin/) - [Rezafungin](https://durgical.com/en/pharmacology/rezafungin/) - [Ibrexafungerp](https://durgical.com/en/pharmacology/ibrexafungerp/) - [Flucytosine](https://durgical.com/en/pharmacology/flucytosine/) - [Terbinafine](https://durgical.com/en/pharmacology/terbinafine/) - [Griseofulvin](https://durgical.com/en/pharmacology/griseofulvin/) ## Connections ## Related classes 4 - [Polyene antifungals](https://durgical.com/en/pharmacology/classes/polyene-antifungals/) - [Azole antifungals](https://durgical.com/en/pharmacology/classes/azole-antifungals/) - [Echinocandins](https://durgical.com/en/pharmacology/classes/echinocandins/) - [Other antifungals](https://durgical.com/en/pharmacology/classes/other-antifungals/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [DailyMed - AMPHOTERICIN B injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0a54943-9ce4-4f3e-b681-a1a9144c16ce) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - FLUCONAZOLE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0adb2f88-8a6f-4f33-9e2d-73f537e05313) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - CASPOFUNGIN ACETATE injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08fb61ee-a05a-4ce1-934c-8cd26c5733db) (DailyMed (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/antifungal-therapy-fungal-biology-and-drug-targets/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/antifungal-therapy-fungal-biology-and-drug-targets/