Malassezin—a novel agonist of the Arylhydrocarbon receptor from the yeast Malassezia furfur

• Published in: Bioorganic & medicinal chemistry 2001-04, Vol.9 (4), p.955-960
• Main Authors: Wille, Gregor, Mayser, Peter, Thoma, Wiebke, Monsees, Thomas, Baumgart, Annette, Schmitz, Hans-Joachim, Schrenk, Dieter, Polborn, Kurt, Steglich, Wolfgang
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chromatography, Thin Layer; Cytochrome P-450 CYP1A1 - antagonists & inhibitors; Cytochrome P-450 CYP1A1 - metabolism; Dermatology; Enzyme Inhibitors - pharmacology; Hepatocytes - drug effects; Hepatocytes - enzymology; Indicators and Reagents; Indoles - isolation & purification; Indoles - pharmacology; Malassezia - chemistry; Male; Medical sciences; Models, Molecular; Monophenol Monooxygenase - antagonists & inhibitors; Pigmentary diseases of the skin; Rats; Rats, Wistar; Receptors, Aryl Hydrocarbon - agonists
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(00)00319-9

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50=1.57μM) in rat hepatocytes. Malassezin (1) was isolated from cultures of the yeast Malassezia furfur and synthesized in five steps with 12% overall yield. Compound 1 was found to induce cytochrome P450 as an agonist of AHR (EC50=1.57×10−6 M) in rat hepatocytes.