Staurosporine as an Antifungal Agent

Staurosporine (STS) was discovered in 1977 by Omura and colleagues during a chemical screening for microbial alkaloids. It was the first indolocarbazole compound isolated from a soil-dwelling bacterium, Streptomyces staurosporeus. STS was also found to have antifungal activity, but its potent protein kinase (PK) inhibitory properties, perhaps the most extensively characterized biochemical feature of STS, were only revealed nearly a decade after its discovery. Thereafter, STS has been studied mainly for its anticancer potential with foreseen applications ranging from biomedical (e.g., antiparasitic) to agricultural (e.g., insecticidal). Interestingly, the recent discovery that STS induces apoptosis in the filamentous fungus Neurospora crassa renewed interest in this molecule as a scaffold for antifungal drug development. Studies in fungi and mammalian cell lines suggest that, in addition to PK inhibition, other modes of action are possible for STS. These may involve the targeting of membrane lipid domains and/or alterations of membrane biophysical properties. Here, the studies on the action of STS and its natural and synthetic derivatives against diverse fungal species, since its discovery to the present day, are critically reviewed and discussed with the aim of highlighting their advantages, limitations to be overcome, conceivable mechanisms of action, and potential as antifungal chemotherapeutic agents.