title: Pityriarubins, novel highly selective inhibitors of respiratory burst from cultures of the yeast Malassezia furfur: comparison with the bisindolylmaleimide arcyriarubin A.
abstract: Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the pathophysiology of the disease. We here report that the novel pityriarubins A, B and C, isolated from cultures of the yeast, inhibit respiratory burst in human neutrophils, activated by various agents, in a highly selective, unexpected manner. The release of 5-lipoxygenase products after challenge of neutrophils with the calcium ionophore A23187 is also inhibited in a dose-dependent manner. These activities reflect the close structural relationship of pityriarubins to bisindolylmaleimides, which have recently gained great interest as protein kinase inhibitors.
authors.affiliation: Center of Andrology and Dermatology, Justus Liebig-Universität, Gaffkystrasse 14, 35385 Giessen, Germany. kraemer@innere.med.uni-giessen.de
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Krämer
authors.forename: Dino
authors.initials: D
authors.lastname: Kessler
authors.forename: Ute-Christina
authors.initials: UC
authors.lastname: Hipler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Irlinger
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hort
authors.forename: Rolf-Hasso
authors.initials: RH
authors.lastname: Bödeker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Steglich
authors.forename: Peter
authors.initials: P
authors.lastname: Mayser
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D006801:Humans; D026121:Indole Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008290:Malassezia / Q000737:chemistry*; D008301:Maleimides / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D014010:Tinea Versicolor / Q000209:etiology
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; D008301:Maleimides; C514964:pityriarubin A; C514962:pityriarubin B; C514963:pityriarubin C; D001094:Arachidonate 5-Lipoxygenase; C088060:bisindolylmaleimide