Chem. Pharm. Bull. 53(8) 907—910 (2005)

consists of 85 species, occurring mainly in Iran and westward to Syria, Turkey and Europe. It is represented in Pakistan by 8 species. Onosma hispida WALL. is a perennial herb up to 70 cm tall with a prominent taproot, it is widely distributed in the northern areas of Pakistan. The plant has cooling, laxative, anthalminitic and alexipharmic effects, and is also used to treat diseases of the eye, derangements of the blood, bronchitis, abdominal pain, stangury, thirst, itch, leucoderma, fever, wounds, piles and in urinary calculi. Its flowers are prescribed as a stimulant and cardiac tonic in rheumatism and diseases of heart. The plant is used as a dye for wool, hair and also imparts a rich red colour to medicinal oil and fats. Previously, aliphatic ketone, lipids, naphthazarins, alkaloids, shikonin, phenolic constituents and naphthoquinones have been reported from the genus Onosma. Our previous work on O. hispida has resulted in the isolation of cholinesterase inhibitory flavanone. However, the crude ethanolic extract and the subsequent hexane fraction also showed lipoxygenase inhibitory activity. This prompted us to carry out further phytochemical studies on this plant. Herein we report the isolation and structural elucidation of onosmins A (1) and B (2), lipoxygenase inhibitors, along with the known compounds apigenin (3), 6,4 -dimethoxy-3,5,7trihydroxyflavone (4), 6,7-dimethoxy-3,5,4 -trihydroxyflavone (5) and apigenin 7-O-b-D-glucoside (6). Lipoxygenases (LOX, EC 1.13.11.12) constitute a family of non-haem iron containing dioxygenases that are widely distributed in animals and plants. The non-haem iron serves as a catalytic center for the stereoand regio-specific dioxygenation of select carbon atoms in polyunsaturated fatty acids containing a 1,4-pentadiene motif. Linoleic acid is the primary substrate of the plant LOXs, while the mammalian isozymes mainly catalyze the metabolism of arachidonic acid. In mammalian cells, LOX are key enzymes in the biosynthesis of many bioregulatory compounds such as hydroxyeicosatetraenoic acids (HETEs), leukotrienes, lipoxins and hepoxylines. It has been found that these LOX products play a role in a variety of disorders such as bronchial asthma and inflammation, and also have a profound influence on the development of several human cancers. LOX are therefore a potential target for the rational drug design and discovery of mechanism-based inhibitors for the treatment of bronchial asthma, inflammation, cancer and autoimmune diseases. Compounds 1 and 2 showed significant inhibitory activity against lipoxygenase enzyme.