Pityriarubins, novel highly selective inhibitors of respiratory burst from cultures of the yeast Malassezia furfur: comparison with the bisindolylmaleimide arcyriarubin A.
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.
Krämer
Hans-Joachim
HJ
Center of Andrology and Dermatology, Justus Liebig-Universität, Gaffkystrasse 14, 35385 Giessen, Germany. kraemer@innere.med.uni-giessen.de
Kessler
Dino
D
Hipler
Ute-Christina
UC
Irlinger
Bernhard
B
Hort
Wiebke
W
Bödeker
Rolf-Hasso
RH
Steglich
Wolfgang
W
Mayser
Peter
P
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
D026121:Indole Alkaloids; D007211:Indoles; D008301:Maleimides; C514964:pityriarubin A; C514962:pityriarubin B; C514963:pityriarubin C; D001094:Arachidonate 5-Lipoxygenase; C088060:bisindolylmaleimide