title: Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents.
abstract: A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14alpha-demethylase (14DM) and delta24-sterol methyltransferase (24-SMT) based on the common characteristic features of 24-aminosterols and azole antifungal agents, were synthesized and evaluated for their antifungal activities and inhibitory activities of 14DM and 24-SMT. Among these compounds, imidazolylmethyloxolane derivatives 28a and 28b showed potent in vitro antifungal activities comparable to those of itraconazole. However, the in vitro bioactivities have not been linearly translated into in vivo protection data for some unknown reasons.
authors.affiliation: Department of Chemistry, Pohang University of Science & Technology, South Korea. skchung@chem.postech.ac.kr
authors.forename: S K
authors.initials: SK
authors.lastname: Chung
authors.forename: K W
authors.initials: KW
authors.lastname: Lee
authors.forename: H I
authors.initials: HI
authors.lastname: Kang
authors.forename: C
authors.initials: C
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Kudo
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D065607:Cytochrome P-450 Enzyme Inhibitors; D015195:Drug Design; D004875:Ergosterol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D008861:Microsomes / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D051381:Rats; D058886:Sterol 14-Demethylase; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D014230:Triazoles; D010088:Oxidoreductases; C548415:Cyp51 protein, mouse; D058886:Sterol 14-Demethylase; D004875:Ergosterol