Ergosterol system

The ergosterol system mentioned earlier falls in this category. Before the system is discussed, it is worthwhile to point out that, in general, substitution of even a simple group such as an alkyl seems to change the details of the photochemical primary processes in a startling manner among the dienes and trienes. Thus, in solution, 1,3,5-hexatriene cannot be converted to 1,3-cyclohexadiene photochemically, but 2,4,6-octatriene does cyclize photochemically to (rans-5,6-dimethyl-l,3 Cyclohexadiene under the same conditions. ... 

The tachysterol/ergosterol system continues to attract considerable interest. A typical result has shown that the triols (122) can be transformed on irradiation in ether/THF into Previtamin analogues which are thermally converted into the... 

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Amphotericin B, is a polyene antibiotic, used in the therapy of systemic fungal infections. Its mode of action exploits differences in membrane composition between the pathogen and the human host. Ergosterol, the predominant sterol of fungi, plants, and some protozoan parasites, interacts with Amphotericin B, resulting in an increased ion permeability of the membrane. Humans contain cholesterol, which has a low affinity for amphotericin B. 

A similar strategy can also be used in a seven-step procedure of preparation of 3/3,25-dihydroxy-cholesta-5,7-diene from ergosterol giving a total yield of 30%. The 3-hydroxy function of ergosterol is protected as /-butyldimethylsilyl ether before the 5,7-diene system is treated with l,4-dihydrophthalazine-l,4-dione. In this case, the key step is a very mild method for the cleavage of the hetero Diels-Alder adduct using lithium naphthalenide <1999S1331>. 

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. 

An X-ray crystal structure determination of calciferol (vitamin D-2,71) showed that steric crowding in the s-cis diene system resulted in a twisted conformation with a dihedral angle of 53° [59], On irradiation with a mercury lamp, it was partially converted into ergosterol (72) and tachysterol (73) [60, 61]. When a solution of calciferol in light petroleum containing a trace of iodine was exposed to diffuse daylight, the vitamin was photoisomerized to (74) [62],... 

Ergosterol CjgH OH, a trebly unsaturated alcohol, is derived from the same ring system. It is produced in relatively large amounts by fungi, in particular by yeast, and on irradiation it is isomerised to the anti-rachitic vitamin, vitamin-D (Windaus). 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

Amphotericin-B, an amphoteric polyene macrolide remains the most effective for severe systemic mycoses. It is indicated for systemic mycoses such as disseminated candidiasis, cryptococcosis, aspergillosis, mucormycosis, coccidioidomycosis, histoplasmosis, extracutaneous sporotrichosis and blastomycosis. It is a fungicidal antibiotic without antibacterial activity. It binds to ergosterol in the... 

In addition to the endogenous metabolites, some exogenous sterols possess biological activity similar to that of D3. Ergocalciferol (vitamin D2) is derived from the plant sterol ergosterol and may act as a substrate for both the 25-hydroxylase and the 1-hydroxylase enzyme systems of the liver and kidney to form 25-(OH)D2 and 1,25-(0H)2 D2, respectively. Ergocalciferol (vitamin D2) is the form used in commercial vitamins and supplemented dairy products. Dihydrotachysterol, another sterol that is used as a therapeutic agent, also functions as a substrate for the hydroxylase enzymes in the liver and kidney. 

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... 

Polyporus umbellatus (Pers.) Fr. Zhu Ling (dried fungus) Ergosterol, biotin, protein.33 Diuretic, stimulate the immune system, anticancer. 

PRECURSOR. In biological systems, an intermediate compound or molecular complex present in a living organism which, when activated physiochemically, is converted to a specific functional substance. Sometimes the prefix pro is used to indicate that a compound in question plays the role of a precursor. Examples from the history of vitamin and other essential chemical developments include ergosterol (pro-vitamin D2), which is activated by ultraviolet radiation to form vitamin D carotene (provitamin A) is a precursor of vitamin A prothrombin forms thrombin upon activation in the blood-clotting mechanism. 

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