Study On Synthesis And Activity Evaluation Of Prenyl-Genistein Derivatives

Genistein, a natural isoflavone, exists widely in legumes and rutaceae plants. Genitein shows various bioactivity such as antitumor, antidiabetes. antiviral, antioxidant, anti-inflammatory, et al. Prenylated isoflavonoids are a unique class of naturally occurring flavonoids characterised by the presence of a prenylated side chain (i.e. prenyl, geranyl) on the flavonoids keleton. Although natural prenylated genistein can be elicited from many soybean plants, it is typically obtained as a complex mixture and very small quantities. The situation has prompted explorations directed toward the production of prenylated genistein by chemical synthesis. In this paper, it developed the simple and low-cost procedures to synthesize three series of prenylated isoflavones. The antitumor and inhibition of a-glucosidase of all synthesized products were also investigated. The research will be helpful to the further investigation of prenylated isoflavone-based drugs.The design and synthesis of Lespedeza Ei, Lupiwighteone and Warangalone and their derivatives were started from genistein. Especially, the synthesis of Lespedeza E1 was firstly reported. The synthesis process of Lupiwighteone and Warangalone were optimized. The key steps of our scheme are selective protection and deprotection of hydroxyls, regionselective halogenation and Suzuki coupling reaction. Lupiwighteone and Lespedeza E1 and their derivatives were synthesized starting from genistein by 4-5 steps in 46%-52% overall yields. Warangalone and its derivatives were synthesized starting from genistein in 20%-30% overall yields. The structures of the key intermediates and target compounds were confirmed by ID and 2D-NMRS and LC-MS.Finally, the antitumor activity evaluation of target compounds against leukemia cells (K562), colon cells (HT-29) and gastric cells (MGC-803) indicated that the prenyl groups on the genistein mother core increased the biological activity. The position of free phenol influenced the activity. The evaluation of a-glucosidase inhibitory activity suggested that Lespedeza Ei and Warangalone are higher than the clinical drug acarbose by 10 folds. The docking research indicated that there are more hydrophobic interactions besides hydrogen bonds between a-glucosidase (PDB 3w37) and Lespedeza E1 and Warangalone, respectively. The studies on synthesis and activity of three series of natrual compounds have important significance for structure-activity relationship and new drug development of prenylated isoflavone.