Synthesis And Activities Of Neoflavonoids Derivatives

This paper studies neoflavonoids from the following two aspects including its synthesis and its screening of antidiabetic activity.Various substituted neoflavonoids derivatives including 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins were synthesized by using sulfated Montmorillonite K-10 as a catalyst,which method possessed such advantages as more environmental friendly,more sustainable and economic,simple isolation and purification processes,little byproducts,using earth-abundant catalysts and relativity high yield.The optimum conditions for the reaction were explored in the synthesis of the neoflavonoids skeleton.It was found that the reaction had the highest yield in the nitrobenzene and the optimal H2SO4 concentration was 30% and 5 mmol of the acrylic acid compound required 2g of catalyst.In addition,the catalyst did not significantly reduce the reaction yield after repeated use of 5 times.In the part of the synthesis of neoflavonoids,this paper explored the catalytic reduction of demethylation of aluminum iodide to modify the compounds.Notably,the yield of this demethylating reaction was more than 90% without complex purification.Those neoflavonoids derivatives were screened for antioxidant,a-glucosidase inhibitory,aldose reductase 2(ALR2)inhibitory and advanced glycation end-products(AGEs)formation inhibitory.Most compounds exhibited significant antioxidant and advanced glycation end-products formation inhibitory activities.Among them,compounds 8k,8l,8m and 8n not only have excellent performance in the above three aspects,but also have strong ?-glucosidase inhibitory activity,the results showed that the double bond between C3 and C4 is necessary to inhibit ?-glucosidase,and also is effective for free radical scavenging activity and inhibition of glycosylated end products.It was interesting to note that out of thirty-one compounds,8k and 8l were found to have greater ALR2 inhibitory activity than the standard drug quercetin.On the basis of this,the compounds 8l,8m and 8n were selected to carry out acute toxicity and antidiabetic activity in mice.First of all,oral toxicity experiments showed that the lethal dose of 50 % of these three compounds was greater than 5000 mg / kg,so they were not deleterious to mice.And then through the acute hypoglycemic assay of normal mice and acute antihyperglycemic assay of diabetic mice to choose compounds and the most appropriate dosage.Thereafter,the target compounds 8l,8m(30mg/ml)and glibenclamide were administered once on a daily,for a period of 16 days,to STZ-induced diabetic mice.The results showed that these two compounds could significantly reduce the blood glucose level of diabetic mice,reduce the weight loss of mice,and improve the level of impaired glucose tolerance.Antidiabetic activity studies had shown that compounds 8l and 8m were found to be equipotent to the standard drug glibenclamide in vivo.In summary,the target compound 8l provided a potential drug design concept for the development of multi-target antidiabetic and its complications of potential drugs.The whole experiment showed that antidiabetic activity is prevalent in neoflavonoids,which added a new natural skeleton to the development of antidiabetic active drugs.