Diphenyl ethers from the cultured lichen mycobiont of Zahlbr.

Purpose: Cultured lichen mycobionts are valuable sources of new natural compounds. Mycobiont of growing in Vietnam was isolated, cultivated and chemically investigated. The crude extract of this cultured mycobiont showed potent alpha-glucosidase inhibition with an IC value of 50 μg/mL.

Methods: Multiple chromatographic methods were applied to the extract to isolate compounds. The combination of Nuclear Magnetic Resonance analysis and high-resolution mass spectroscopy determined their chemical structures. Electrophilic bromination/chlorination was applied to obtain new derivatives using NaBr/HO and NaCl/HO reagents. Compounds were evaluated for enzyme inhibitory activities, including alpha-glucosidase inhibition, HIV-1 reverse transcriptase inhibition, SARS-CoV-2 main protease (M) inhibition, anti-inflammatory activity, and cytotoxicity against several cancer cell lines. A molecular docking study for -SARS-CoV-2 was conducted to understand the inhibitory mechanism.

Results: A new diphenyl ether, handelone () and a known compound xylarinic acid A () were isolated and elucidated. Four synthetic products 6'-bromohandelone (), 2'-bromohandelone ), 2',6'-dibromohandelone , and 2',6'-dichlorohandelone () were prepared. Compound showed good activity against M with an IC value of 5.2 μM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.

Conclusion: A new compound, handelone () was isolated from the cultured mycobiont of . From these compounds, four new derivatives were prepared. Compound showed good activity against M with an IC value of 5.2 μM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.