alexa Biochemical basis for the activity and selectivity of oral antifungal drugs.


Internal Medicine: Open Access

Author(s): Vanden Bossche H, Marichal P, Gorrens J, Coene MC

Abstract Share this page

Abstract The ergosterol biosynthesis-inhibiting (EBI) antifungals constitute the most important group of compounds developed for the control of fungal diseases in man. Currently, representatives of two classes of EBI antifungals are available: the squalene epoxidase inhibitors and those that interfere with cytochrome P450-dependent ergosterol synthesis. The allylamines (eg, terbinafine) inhibit squalene epoxidase in sensitive fungi, Trichophyton mentagrophytes being the most sensitive species. The most important developments have come from the introduction of the N-substituted imidazoles and triazoles, the so-called azole antifungals. Most of the currently available imidazoles (eg, miconazole, clotrimazole, econazole) and the triazole derivative terconazole are mainly for topical treatment. Ketoconazole was the first azole derivative orally active against yeasts, dermatophytes and dimorphic fungi. The new triazole, itraconazole, appears to be among the most promising orally active systemic agents. All the azole antifungals inhibit the cytochrome P450-dependent, 14 alpha-demethylase, a key enzyme in the synthesis of ergosterol, the main sterol in most fungal cells. Of all the azoles tested, itraconazole shows the highest affinity for the cytochrome P450 involved. It is about three and ten times more active in vitro than miconazole and the bis-triazole, fluconazole, respectively. Itraconazole's high affinity for the fungal P450 originates from its triazole group as well as from the nonligating lipophilic tail.
This article was published in Br J Clin Pract Suppl and referenced in Internal Medicine: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version