Prenylated dihydrostilbenoid derivatives from the aerial parts of Glycyrrhiza uralensis and their potent antibacterial activity against drug-resistant clinical isolates.

A phytochemical investigation of the aerial parts of Glycyrrhiza uralensis led to the isolation of thirteen previously undescribed compounds (1-13), comprising one dihydrophenanthrene, prenyluralensol A, and twelve dihydrostilbenoids, prenyluralensols B-M, together with seven known analogues (14-20). Their structures were established by extensive spectroscopic analyses and electronic circular dichroism calculations. Compound 1 is noteworthy as the first example of a dihydrophenanthrene derivative incorporating three pyran rings. The antimicrobial evaluation showed that seven compounds (3, 7, 8, 12, 13, 17, and 18) exhibited activity against clinically relevant drug-resistant bacteria, including vancomycin-resistant Enterococcus faecium 36235, methicillin-resistant Staphylococcus aureus USA300, and multidrug-resistant Helicobacter pylori Hp159, with minimum inhibitory concentration (MIC) values of 2-4 μg/mL. Among them, 7 displayed inhibitory activity against both Gram-positive and Gram-negative resistant strains. A preliminary analysis of structure-activity relationships suggested that antibacterial activity is influenced by substitution at the C-3' position and may be enhanced by the presence of a C-5-linked prenyloxy group. This study expands the chemical diversity of naturally occurring prenylated dihydrostilbenoids and provides insights into structural features relevant to antibacterial activity.