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Review

Staurosporine as an Antifungal Agent

by
Filipa C. Santos
,
Joaquim T. Marquês
,
Eva N. Santos
and
Rodrigo F. M. de Almeida
*
Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(19), 9683; https://doi.org/10.3390/ijms26199683 (registering DOI)
Submission received: 25 August 2025 / Revised: 23 September 2025 / Accepted: 24 September 2025 / Published: 4 October 2025
(This article belongs to the Section Molecular Microbiology)

Abstract

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.
Keywords: antimycotic activity; indolocarbazole; mode of action; pathogenic fungi; drug-resistant fungal infections; protein kinase inhibitors; fungal plasma membrane; fluorescent alkaloid; sphingolipid-enriched domains (SLEDs) antimycotic activity; indolocarbazole; mode of action; pathogenic fungi; drug-resistant fungal infections; protein kinase inhibitors; fungal plasma membrane; fluorescent alkaloid; sphingolipid-enriched domains (SLEDs)

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MDPI and ACS Style

Santos, F.C.; Marquês, J.T.; Santos, E.N.; de Almeida, R.F.M. Staurosporine as an Antifungal Agent. Int. J. Mol. Sci. 2025, 26, 9683. https://doi.org/10.3390/ijms26199683

AMA Style

Santos FC, Marquês JT, Santos EN, de Almeida RFM. Staurosporine as an Antifungal Agent. International Journal of Molecular Sciences. 2025; 26(19):9683. https://doi.org/10.3390/ijms26199683

Chicago/Turabian Style

Santos, Filipa C., Joaquim T. Marquês, Eva N. Santos, and Rodrigo F. M. de Almeida. 2025. "Staurosporine as an Antifungal Agent" International Journal of Molecular Sciences 26, no. 19: 9683. https://doi.org/10.3390/ijms26199683

APA Style

Santos, F. C., Marquês, J. T., Santos, E. N., & de Almeida, R. F. M. (2025). Staurosporine as an Antifungal Agent. International Journal of Molecular Sciences, 26(19), 9683. https://doi.org/10.3390/ijms26199683

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