Staurosporine as an Antifungal Agent

Author: mycolabadmin
10/4/2025
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Summary

Staurosporine is a natural compound produced by soil bacteria that can kill fungi. Scientists originally discovered it in 1977 and found it works by blocking proteins called kinases that fungi need to survive. Recent research shows it could be useful against drug-resistant fungal infections, especially when combined with other antifungal medicines. However, it needs to be modified to make it safer for human use.

Background

Staurosporine (STS) is an indolocarbazole alkaloid first isolated in 1977 from Streptomyces staurosporeus. While originally recognized for antifungal activity, it gained prominence for its potent protein kinase inhibitory properties and anticancer potential. Recent studies have renewed interest in STS as a scaffold for antifungal drug development due to its ability to induce apoptosis in fungi and other bioactive properties.

Objective

This review critically examines the antifungal properties of staurosporine and its natural and synthetic derivatives against diverse fungal species from discovery to present day. The aim is to highlight advantages, limitations, conceivable mechanisms of action, and potential of these compounds as antifungal chemotherapeutic agents to address drug-resistant fungal infections.

Results

STS demonstrates broad-spectrum antifungal activity against both phytopathogens and human fungal pathogens, with MIC values ranging from 0.02 to 50 μg/mL depending on the fungal species and methodology. Several STS analogues show improved antifungal potency compared to the parent compound. STS exhibits synergistic effects with conventional antifungals like fluconazole and caspofungin, and operates through multiple mechanisms including protein kinase inhibition, calcium mobilization, and membrane lipid domain targeting.

Conclusion

Staurosporine and its derivatives show significant promise as antifungal agents, particularly through combination therapies and as scaffolds for novel drug development. While protein kinase inhibition is a primary mechanism, additional modes of action involving membrane lipid domains warrant further investigation. Strategies to improve selectivity and reduce toxicity are essential for clinical translation of these compounds.

Published in:International Journal of Molecular Sciences,
Study Type:Review,
Source: PMID: 41096950, DOI: 10.3390/ijms26199683