Mycotoxins, antifungalsAntifungals are a group of drugs that are effective against human-pathogenic fungi, i.e. fungi that attack humans and cause mycosis (fungal disease). The effect of antimycotics is based on the fact that they act against or on fungus-specific structures. Since the fungal cells are structured in some places similar to human cells, there is a manageable number of points of attack for antimycotics.

These targets are usually located in the cell membrane of the fungi. Depending on what kind of fungus causes the mycosis, other antimycotics are used. Not every antimycotic is effective on every fungus, because as with bacteria, there are natural resistances.

Classification of antimycotics

The antimycotics can be classified according to their mode of action. On the one hand they can be fungicidal – the fungal cells are killed by the respective antimycotic, or they are fungostatic. This means that the fungal cells cannot continue to grow and multiply in the organism of the infected person. A further classification can be made according to the type of application: local (the antimycotic only works on the treated area, e.g. the skin) or systemic (the antimycotic works in the whole organism).

Active substances and modes of action

The azoles are a large group. They are divided into the subgroup of triazoles and imidazoles. The classification depends on how many nitrogen atoms are in the heterocyclic ring.

This heterocyclic ring is a chemical structure which can be found in all azoles. While a triazole has three nitrogen atoms, an imidazole has only two in the heterocyclic ring. The effect of the azoles is based on the disturbance of the ergosterol synthesis.

Ergosterol is similar to cholesterol in humans. It is a sterol (membrane lipid) which is essential for the formation of the cell membrane of fungi. The azoles inhibit a specific enzyme (14?

sterol demethylase), which plays a central role in the formation of ergosterol. The lack of formation of ergosterol therefore causes a deficiency. This leads to membrane damage to the fungal cells.

As a result, the fungal cells do not die immediately, but they cannot multiply and grow further – azoles are fungostatic. Depending on the proven fungal infection and the location of the infection, different azoles can be used. For example, care must be taken to ensure that fluconazole has no effect on aspergilla and certain strains of candida.

Another group of active ingredients are polyene macrolides. These include nystatin, natamycin and amphotericin B. Amphotericin B binds to ergosterol and is incorporated into the cell membrane. This makes the cell membrane more permeable for components from the fungal cell – the membrane no longer functions efficiently.

As a result, the fungal cell dies (fungicide). Amphotericin B has acute and chronic side effects, which in some places limit the therapy. Today a modified preparation is available – the liposomal Amphotericin B.

This shows fewer side effects, but also costs considerably more money. Another group are the echinocandins (caspofungin, micafungin). These act by inhibiting glucan synthesis (a glucose chain specific to the fungus).

The glucan is relevant for the stability of the cell wall. By inhibiting its synthesis, the cell wall loses the stability otherwise produced by glucan. Echinocandins are fungicidal or fungostatic, depending on the fungus on which they act.

Furthermore the group of pyrimidine derivatives (flucytosine) is available. The flucytosine is taken up by fungal cells and enzymatically converted into 5-fluorourcail. Its effect is based on the inhibition of protein and DNA synthesis. This inhibition causes the metabolism of the fungal cell to break down – the pyrimidine derivatives are fungicidal and fungostatic.