Detail of "22916-47-8"

Reference

Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: the inhibition of isoprenoid biosynthesis

Correction of: Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: the inhibition of isoprenoid biosynthesis. Vanden Bossche, Hugo; Lauwers, Wim; Willemsens, Gustaaf; Marichal, Patrick; Cornelissen, Frans; Cools, Willy (Dep. Comp. Biochem., Janssen Pharm. Res. Lab., Beerse B-2340, Belg.). Pestic. Sci., 15(2), 188-98 (English) 1984. CODEN: PSSCBG. ISSN: 0031-613X. DOCUMENT TYPE: Journal CA Section: 5 (Agrochemical Bioregulators) The antimycotic N-substituted imidazoles and triazoles, such as imazalil [35554-44-0], ketoconazole [65277-42-1], and itraconazole [84625-61-6], interfere selectively at low concns. (30.01 nM) with the 14a-demethylase system (which is dependent on cytechrome P 450 [9035-51-2] of fungal cells, for example, Candida albicans and Penicillium italicum. This results in a decreased availability of ergosterol [57-87-4] and the accumulation of 14a-methyl-sterols such as lanosterol [79-63-0]. Cholesterol [57-88-5] synthesis in a subcellular fraction of rat liver, in intact fibroblasts, and in vivo in rat liver, was much less sensitive, for example, to ketoconazole. The imidazole derivs. imazalil, miconazole [22916-47-8], ketoconazole, and parconazole [61400-59-7], and the triazole derivs. propiconazole [60207-90-1], terconazole [67915-31-5], and triaconazole affect the cytochrome P 450 species of microsomal fractions from Saccharomyces cerevisiae and rat liver. Cytochrome P 450 of rat-liver microsomes was much less sensitive to these azole derivs., in parallel with the lower sensitivity of cholesterol synthesis. Using unilamellar vesicles composed of phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylcholine, multilamellar vesicles of dipalmitoylphosphatidylcholine, and intact S. cerevisiae, the substitution of ergosterol by lanosterol leads to functional changes in the membranes. The selective interaction of the azole derivs. with the yeast microsomal cytochrome P 450 leads to the accumulation of 14a-methyl-sterols and results in changes in the permeability of the membranes and leakages. The obsd. inhibition of growth may have its origin in these changes. Miconazole, ketoconazole and deacylated ketoconazole (R-39519) [67914-61-8] also affect the growth of Staphylococcus aureus, miconazole being 12.5 and 14 times, resp., more active than R-39519 and ketoconazole. The greater antibacterial activity of miconazole coincides with its greater inhibition of the biosynthesis of C-55 isoprenoid alc. and vitamin K. The phosphorylated deriv. of C-55 isoprenoid alc. has functional importance in the biosynthesis of bacterial cell wall and membrane polymers, and the menaquinone vitamin K plays a role in the electron transport of Gram-pos. bacteria. The reduced synthesis of these vital compds. may contribute to the antibacterial activity of miconazole.

Efficacy of antifungal agents in the cornea

Efficacy of antifungal agents in the cornea. II. Influence of corticosteroids. O'Day, Denis M.; Ray, Wayne A.; Robinson, Richard; Head, W. Steven (Sch. Med., Vanderbilt Univ., Nashville, TN 37232, USA). Invest. Ophthalmol. Visual Sci., 25(3), 331-5 (English) 1984. CODEN: IOVSDA. ISSN: 0146-0404. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 The influence of topical corticosteroid on the efficacy of 5 topical antifungal agents was evaluated in a standardized rabbit model of Candida keratitis using a quant. mycol. technique. Topical 1% prednisolone [50-24-8] worsened the disease when given alone and adversely influenced the efficacy of 5% natamycin [7681-93-8], 1% flucytosine [2022-85-7], and 1% miconazole [22916-47-8] when given in combination. The efficacy of amphotericin B [1397-89-3] appeared unaffected when the antifungal agent was administered in concns. of 0.5% and 0.15%. Ketoconazole [65277-42-1] was completely ineffective. The adverse effect of the topical corticosteroid appeared to be inversely related to the efficacy of the antifungal agent in vivo.