Gunacins: Novel Benzo[<i>g</i>]chromene Derivatives from the Fungus <i>Exobasidium</i> sp. and Their Potent Anti-<i>Leishmania</i> and <i>Trypanosoma</i> Activities
Six new pyranonaphthoquinone derivatives, gunacin A-E (<b>2-7</b>), along with the known compounds gunacin (<b>1</b>) and the isocoumarin derivative (+) orthosporin (<b>8</b>), 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 (<b>1</b>, <b>5</b>) demonstrated high activity against Leishmania mexicana and four salivarian Trypanosoma species, with the lowest detected EC<sub>50</sub> value of 0.02-0.24 μM, a value that is comparable to those of currently used drugs. In addition, compounds <b>1</b>, <b>3</b>, <b>5</b>, <b>6</b>, and <b>7</b> demonstrated antibacterial properties at micromolar concentrations, while <b>1</b>, <b>5</b>, <b>6</b>, and <b>7</b> 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 (EC<sub>50</sub> = 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.
Authors
- Jaroslav Semerád (ORCID: https://orcid.org/0000-0002-6470-183X)
- Alena Zı́ková (ORCID: https://orcid.org/0000-0002-8686-0225)
- Jakub Zápal
- Miroslav Flieger (ORCID: https://orcid.org/0000-0002-1156-0404)
- Martina Slapničková (ORCID: https://orcid.org/0000-0003-4449-6717)
- Martin Štícha (ORCID: https://orcid.org/0000-0001-8008-7668)
- Tomáš Vomastek (ORCID: https://orcid.org/0000-0002-4071-0432)
- Marc Stadler (ORCID: https://orcid.org/0000-0002-7284-8671)
- Eva Stodůlková (ORCID: https://orcid.org/0000-0002-1801-5038)
- Zuzana Klímová (ORCID: https://orcid.org/0009-0007-9416-2455)
- Jan Černý (ORCID: https://orcid.org/0000-0002-5624-2215)
- Marek Kuzma (ORCID: https://orcid.org/0000-0001-7415-2734)
- Tomáš Cajthaml (ORCID: https://orcid.org/0000-0002-3393-1333)
- Ivana Cı́sařová (ORCID: https://orcid.org/0000-0002-9612-9831)
- Adéla Čmoková (ORCID: https://orcid.org/0000-0002-7986-6688)
- Valéria Grobárová (ORCID: https://orcid.org/0000-0002-1978-0065)
- Miroslav Kolařík (ORCID: https://orcid.org/0000-0003-4016-0335)
- Eva Cséfalvay (ORCID: https://orcid.org/0000-0002-9297-2784)
- Andrej Jašica
- Winnie Cherotich Maritim (ORCID: https://orcid.org/0009-0006-5611-8712)
- Dominik Lovás
- Tereza Ježková
Institutions
- Egerton University (KE)
- Czech Academy of Sciences (CZ)
- Charles University (CZ)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Helmholtz Centre for Infection Research (DE)
- Institute of Parasitology (CZ)
- Czech Academy of Sciences, Biology Centre (CZ)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1021/acsomega.5c01325
- Citations
- 1
- Primary Topic
- Phytochemical compounds biological activities
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Grantová Agentura, Univerzita Karlova
- European Commission
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- Akademie Věd České Republiky
- Mikrobiologický Ústav, Akademie Věd České Republiky
- H2020 European Research Council
- H2020 Marie Skłodowska-Curie Actions