Ergosterol synthesis and

Cytoplasmic membrane Polymyxins Polyenes Imidazoles and triazoles Naftidine Disrupt bacterial membranes Disrupt fungal membranes Inhibit ergosterol synthesis Inhibits ergosterol synthesis Bind to LPS and phospholipids Bind preferentially to ergosterol Pathway not in mammalian cells Pathway not in mammalian cells... 

Fluconazole and itraconazole are newer, orally effective triazole derivatives. The topically active allylamine naftidine and the morpholine amorolfine also inhibit ergosterol synthesis, albeit at another step. 

Mechanism of Action An antifungal agent that inhibits ergosterol synthesis. Therapeutic Effect Destroys cytoplasmic membrane integrity of fungi. Fungicidal. Pharmacokinetics Low systemic absorption. Absorbed and distributed in each layer... 

Ergosterol, the predominant sterol in yeast cells, plays an important role in membrane fluidity, permeability and the activity of many membrane-bound enzymes. In terpene-treated cells, ergosterol synthesis was strongly inhibited, and a global upregulation of genes associated with the ergosterol biosynthesis pathway was described in response to terpene toxicity [80, 121]. 

Ketoconazole Blocks fungal P450 enzymes and interferes with ergosterol synthesis Poorly selective interferes with mammalian P450 function Broad spectrum but toxicity restricts use to topical therapy Oral, topical Toxicity and interactions Interferes with steroid hormone synthesis and phase I drug metabolism... 

The principle action of the DMI fungicides is to inhibit the action of the cytochrome 450-dependent removal of the 14a-methyl group from 24-methylene dihydrolanosterol. The resulting accumulation of the substrate 24-methylene dihydrolanosterol, obtusifoliol and 14a-methyl-fecosterol, together with the consequent reduction in ergosterol synthesis, disrupts the normal functioning of cell membranes and was thought to be the basis of DMI activity. 

Ergosterol biosynthesis inhibitors differ in their molecular modes of action. This is especially true for the morpholine derivative tride-morph and fenpropimorph. In Pyricularia oryzae, tridemorph inhibits the A to A7 -isomerization reaction in ergosterol synthesis,... 

Amphotericin B preferentially damages ergosterol-containing membranes fluconazole and several congeners are inhibitors of ergosterol synthesis. 

The mechanism of action of this group is well studied. These compounds effect fungal metabolism by inhibiting ergosterol synthesis. This compound is an important component of the cell membrane, and its absence leads to al-... 

The principal action of the azole group is to destabilize the fungal cell wall by inhibiting ergosterol synthesis in the cell membrane. In addition, they variably bind to and inhibit mitochondrial... 

These two drugs are used topically to treat skin and nail infections. They interfere with ergosterol synthesis. Their use is discussed in Chapter 8. 

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