Prenylflavonoids Isolated From Artocarpus Nigrifolius And Their ?-glycosidase Inhibitory Activities

Alpha-Glucosidase Inhibitors?AGIs?are a class of oral drugs that reduce the blood sugar concentration of diabetic patients by delaying the absorption of intestinal carbohydrate compounds,and are widely used in the treatment of postprandial hyperglycemia Type 2diabetes.AGIs can prevent and improve the occurrence of diabetes complications to a certain extent.Compared with other types of anti-diabetic drugs,AGIs have less toxic and side effects on liver and kidney functions,and the efficacy is long-lasting and mild.It can effectively control patients'postprandial hyperglycemia and has good tolerance.Therefore,AGIs inhibitors have good development prospects and play an extremely important role in the treatment of diabetes.Natural products are an important source of AGIs.The three AGIs currently on the market are directly or indirectly derived from natural products.In recent years,research on natural-derived AGIs is flourishing.More and more active natural product molecules with?-glucosidase inhibitory activities have been discovered.These molecules cover various types of natural product skeleton types such as prenylated flavonoids.In our early phytochemical research on the Artocarpus plant A.nigrifolius,15isopentenyl flavonoids has been isolated,and most of them show potent proliferative activities toward two human cancel cell lines SiHa and SGC-7901.Isoprenyl flavones have been reported with potent?-glucosidase inhibitory activities.In order to find AGIs from natural product sources and further explore the medicinal value of A.nigrifolius,we re-enriched and separated the isoprenyl flavonoids of A.nigrifolius.Using MCI column chromatography,silica gel column chromatography,Sephadex LH-20 gel column chromatography and reversed-phase semi-preparative HPLC,a total of eight isopentenyl flavonoids were isolated,including one new compound 5,7-dihydroxy-2-?4-hydroxybenzoyl?-4H-benzo[d][1,3]dioxin-4-one?1?and seven known isoprenylflavonoids,namely,2,4,2?,4?-tetrahydroxy-3-?3-methyl-2-butenyl?-chalcone?2?,artocarmin B?3?,artocarmin C?4?,6-prenyl-4',5,7-trihydroxyflavone?5?,artocarpesin?6?,gemichalcone B?7?and artocarpusin A?8?.Above eight compounds were evaluated their?-glucosidase inhibitory activities together with five analogues isolated previously by our group.The results showed that compound 8(IC₅₀ 5.46±0.80?M)had the best inhibitory effect and was significantly stronger than the positive control acarbose,while the activities of compounds 2,3 and 9 are comparable to the positive control.Therefore,these isoprenyl flavonoids can be used as potential AGIs for further research and utilization.