Molecular Networking-Guided Isolation and Bioactivity of β-Acid Derivatives from Hops

Through targeted isolation guided by feature-based molecular networking, nine previously undescribed β-acids, designated lupulxinones A–I ( 1 – 9 ), were obtained from the female inflorescences of hops ( Humulus lupulus L.). Their structures were elucidated through comprehensive spectroscopic analysis, and the absolute configurations were established by electronic circular dichroism calculation together with X-ray single-crystal diffraction. Notably, lupulxinones A and B ( 1 – 2 ) are rare oxidized β-acids possessing a 5/5/6/5 tetracyclic scaffold with an embedded tetrahydrofuran ring that precludes enol interconversion. Additionally, lupulxinones A and B were separated into their respective enantiomers using a chiral chromatographic column. The biological evaluation revealed that compounds 3, 5, and 8 exhibited antibacterial activity against Cutibacterium acnes, with 8 displaying the most potent antiacne activity (MIC = 1.56 μg/mL; MBC = 3.13 μg/mL). Moreover, 1a and 3 showed moderate inhibition of LPS-induced nitric oxide production in RAW264.7 macrophages at 100 μM. Collectively, these findings suggest that hop extracts hold therapeutic promise for acne treatment.