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.