Abstract
Phenalenone derivatives sourced from fungi are polyketides that have attracted significant interest because of their diverse chemical structures and potential bioactivities. As part of our ongoing quest to discover novel natural products with biological properties from diverse natural resources, three unreported phenalenone derivatives (1–3), named ent-12-methoxyisoherqueinone (1), (−)-scleroamide (2), and (+)-scleroamide (3), together with four known phenalenone derivatives, ent-atrovenetinone (4), isoherqueinone (5), herqueinone (6), and ent-peniciherquinone (7) were isolated from the Hawaiian soil fungus Penicillium herquei FT729, collected on the Big Island, Hawaii. Compounds 2 and 3 were enantiomers, which were separated using a chiral-phase HPLC column, which provided optically pure compounds 2 and 3. The structures of the novel compounds were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution ESIMS. Their absolute configurations were determined using quantum chemical electronic circular dichroism (ECD) calculations. The inhibitory activity of the isolated compounds (1–7) against indoleamine 2,3-dioxygenase 1 (IDO1) was assessed. Compounds 1, 5–7 inhibited IDO1, with IC50 values of 32.59, 36.86, 19.05, and 24.18 μM, respectively. These findings demonstrated that the phenalenone derivatives 1 and 5–7, as IDO1 inhibitors, are promising anticancer immunotherapeutic agents.
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Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (Grant Nos. 2019R1A5A2027340 and 2021R1A2C2007937) and KRIBB Research Initiative Program (KGM5292113) funded by the Ministry of Science ICT (MSIT) of Republic of Korea.
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Yu, J.S., Jeong, S.Y., Li, C. et al. New phenalenone derivatives from the Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 and their inhibitory effects on indoleamine 2,3-dioxygenase 1 (IDO1). Arch. Pharm. Res. 45, 105–113 (2022). https://doi.org/10.1007/s12272-022-01372-8
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DOI: https://doi.org/10.1007/s12272-022-01372-8