Bioassay-guided isolation of coumarins and other secondary metabolites from Otostegia fruticosa with antimicrobial activity against multidrug-resistant pathogens

Otostegia fruticosa (Lamiaceae) is an ethnomedicinal shrub traditionally used for cleansing and infection-related ailments in the Horn of Africa and the Arabian Peninsula. This study isolated eight secondary metabolites from the aerial parts: five coumarins—psoralen (1), bergapten (2), umbelliferone (3), prangol (5), and hydroxydecursinol (7); the megastigmane vomifoliol (4); the phenolic acid vanillic acid (6); and the polymethoxylated flavonol galetin 3,6-dimethyl ether (8), all isolated and fully characterised for the first time from the genus Otostegia. The MeOH extract, CH2Cl2 fraction, and purified compounds were evaluated by broth microdilution against multidrug-resistant pathogens, including MDR A. baumannii and C. auris. The CH2Cl2 fraction showed broad-spectrum bactericidal and fungicidal activity, while the MeOH extract was selectively bacteriostatic against MDR A. baumannii. Psoralen (1) and galetin 3,6-dimethyl ether (8) were principal contributors, with compound 8, for the first time, exhibiting potent fungicidal activity against C. auris.