A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. mode of Action
| Autor: | Mikio Arisawa, Yuzuru Sekine, Noboru Nakayama, Yuri Sudoh, Hisao Shimada, Masumi Kondoh, Toshikazu Yamazaki, Yuhko Aoki |
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| Rok vydání: | 1992 |
| Předmět: |
Stereochemistry
Glycine Microbial Sensitivity Tests Biology Fungal Proteins Lanosterol Sterol 14-Demethylase chemistry.chemical_compound Candida albicans Drug Discovery medicine Cytochrome P-450 Enzyme Inhibitors DNA Fungal Mode of action Heme Pyrans Pharmacology Ergosterol Cytochrome P450 RNA Fungal biology.organism_classification Sterols chemistry Mechanism of action Biochemistry Spectrophotometry biology.protein Demethylase medicine.symptom Oxidoreductases |
| Zdroj: | The Journal of Antibiotics. 45:160-170 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.45.160 |
| Popis: | From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi. |
| Databáze: | OpenAIRE |
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