Ergosterol synthesis inhibition

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... 

Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition... 

Ergosterol synthesis inhibition has been found to coincide with an accumulation of 14 a-methylsterols in yeast cells. The corresponding inhibition in rat liver cells could only be achieved at a sixfold increase in ketoconazole concentration. The enzyme initiating the oxidation of the 14a-CH3 function is lanosterol- 14a-methyldemethylase. It has been... 

The answer is a. (Hardman, p 1180. Katzung, pp 817—819J Fluconazole indirectly inhibits ergosterol synthesis. It inhibits cytochrome P4.50, which is a key enzyme system for cytochrome P4.5O-dependent sterol 14-a-demethylase. This leads to accumulation of 14-a-sterols, resulting in impairment of the cytoplasmic membrane. 

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]. 

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,... 

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... 

Holotoxin Ai inhibits the RNA biosynthesis in Candida albicans and Saccharomyces carlsbergensis, as indicated by the decrease in incorporation of C-uridine to the acid-insoluble fraction of the cells. Similar results were obtained for glycoside fractions of 14 species of Pacific sea cucumbers [132]. Apparently the inhibition of RNA biosynthesis in Saccharomyces carlsbergensis is related to nucleotide loss from yeast cells after treatment with glycosides. Holotoxin Ai also inhibits biosyntheses of squalene, lanosterol and ergosterol in S. carlsbergensis [133]. Mitosis is arrested and DNA synthesis inhibited in onion root bulbs by crude holothurin [134]. 

The fust strongly active, broad spectrum, ergosterol biosynthesis inhibiting fungicide we prepared was 2-(2,4-dichlorophenyl)-l-(l-imidazolyl) hexane, 1, and we began a synthesis program in this area of chemistry in an attempt to obtain an... 

Azoles are fungicidal and interfere with the synthesis of ergosterol by inhibiting the P450-dependent 14 alpha-demethylation of its precursor molecule, lanosterol. 

This group of drugs inhibits an enzyme necessary for ergosterol synthesis. 

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