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. Highly selective inhibitors of ROS release in granulocytes. The bright red pityriarubins A (shown), B and C, isolated from cultures of the yeast Malassezia furfur in presence of tryptophan, structurally resemble the potent protein kinase inhibitors of the aryriarubin A family. They exhibited remarkable selectivity in suppressing granulocytary ROS release with respect to various agents.