Six new pyranonaphthoquinone derivatives, gunacin A-E (2-7), along with the known compounds gunacin (1) and the isocoumarin derivative (+) orthosporin (8), were isolated from the fungus Exobasidium sp. Their chemical structures were elucidated by X-ray crystallography, extensive spectroscopic analysis supported by ROESY experiments, and mass spectrometry. Two tested compounds (1, 5) demonstrated high activity against Leishmania mexicana and four salivarian Trypanosoma species, with the lowest detected EC50 value of 0.02-0.24 μM, a value that is comparable to those of currently used drugs. In addition, compounds 1, 3, 5, 6, and 7 demonstrated antibacterial properties at micromolar concentrations, while 1, 5, 6, and 7 exhibited moderate antifungal activity (MIC 33.3-66.7 μM). In cytotoxicity assays, the compounds exhibited a range of toxicity against mammalian Jurkat, RAT2, MDCK cell lines, HeLa cells, and fibroblasts, with inhibition levels varying from strong to minimal inhibition (EC50 = 0.03-125 μM). This study is among the first to explore Exobasidium, a genus of phytopathogenic fungi and highlights the untapped potential of smut fungi (Basidiomycota: Ustilaginomycetes). The discovery of gunacins, which exhibit potent antiprotozoal activity at submicromolar concentrations, suggests a promising avenue for the development of antiprotozoal agents.
© 2025 The Authors. Published by American Chemical Society.