Sterols fungal cell membrane

This synthetic allylamine derivative inhibits the enzyme squalene epoxidase at an early stage in fungal sterol biosynthesis. Acting as a structural analogue of squalene, naffidine causes the accumulation of this unsaturated hydrocarbon, and a decrease in ergosterol in the fungal cell membrane. 

Pharmacology Ketoconazole, an imidazole broad-spectrum antifungal agent, impairs the synthesis of ergosterol, the main sterol of fungal cell membranes, allowing increased permeability and leakage of cellular components. Pharmacokinetics ... 

MecHanism of Action A fungistatic antifungal that binds to sterols in the fungal cell membrane. Therapeutic Effect Increases fungal cell-membrane permeability, allowing loss of potassium and other cellular components. 

Mechanism of Action. Terbinafine inhibits a specific enzyme (squalene epoxidase) that is responsible for sterol synthesis in the fungal cell membrane. This action impairs cell wall synthesis, with subsequent loss of cell membrane function and integrity. Inhibition of this enzyme causes squalene to accumulate in the fungal cell, which can also impair cell function and lead to death of the fungus. 

Mechanism of Action. Voriconazole inhibits sterol biosynthesis in fungal cell membranes.53 That is, this drug acts like fluconazole and similar agents to impair membrane synthesis, which results in membrane integrity loss and death of the fungal cell. 

Mechanism of Action. Like the systemic azoles, clotrimazole and other topical antifungal azoles work by inhibiting the synthesis of key components of the fungal cell membrane that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids.9 Loss of these components results in the membrane s inability to maintain intracellular homeostasis, leading to death of the fungus. 

The principal polyenes are amphotericin B and nystatin. Amphotericin B is produced by the bacterium Streptomyces nodosus and its activity is due to the ability to bind ergosterol, which is the dominant sterol in fungal cell membranes, and consequently increases membrane permeability by the formation of pores (Fig. 4.4). The action of ampho-... 

Fungal cell membranes are bilayered, consisting primarily of protein and lipid material. They also contain the sterol ergosterol (ca. 6%), an important characteristic not found in bacterial membranes. The cell wall is about 85% carbohydrate, with the remainder being lipid and protein a sterol is woven into this fabric. 

This drug binds to sterol groups in fungal cell membranes and forms channels though the fungal cell membrane. This results in increased permeability and cell death. 

The hydrophilic portions of the molecule align to create a hydrophilic pore in the sterol-containing cell membrane. As a result, there is membrane depolarization and increased membrane permeability and, eventually, fungal cell death. The lipophilic regions of amphotericin B also contribute to its poor solubility in aqueous solutions. The traditional intravenous formulation of amphotericin B includes a dispersing agent, deoxycholate, which facilitates formation of the required micellular dispersion when administered in a 5% dextrose in water solution. 

Morpholine antifungals inhibit ergosterol biosynthesis by acting on the enzymes A -reductase and A ,A -isomerase (Fig. 40.1, Site 3 and 4) (45). Inhibition of these enzymes results in incorporation into fungal cell membranes of sterols retaining either a... 

Some T. have major physiological significance. Thus, lanosterol is converted biosynthetically to cholesterol, the precursor of all steroid hormones, bile acids, and vitamin D3. In fungi, lanosterol is converted to er-gosterol (see sterols), an essential component of the fungal cell membrane. Plant cell membranes also incorporate steroids (phytosterols). In prokaryotes, the hopanoids take over the functions of steroids in the cell membranes. As a component of animal and plant waxes T. strengthen the structures. They protect the plant surface from desiccation and attack by microorganisms (e.g., betulin, lupeol, oleanolic acid, and ursolic acid). 

Sterols were determined by the UV-spectra of the hexane-extract of the saponified wet cells. Fatty acid composition was measured by capillary gas-chromatography on PEG-1000stationary phase. The ion permeability of the fungal cell membrane was measured by a conductometric method with water-washed, ion-free mycelia. 

Azole derivatives currently available for oral treatment of systemic mycosis include fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and others. As discussed in Chapter 48, imidazole derivatives act by affecting the permeability of the cell membrane of sensitive cells through alterations of the biosynthesis of lipids, especially sterols, in the fungal cell. 

---