Synthesis, α-Glucosidase Inhibition And Promotion Angiogenesis Effect Of Chrysin Coupled To NO Donors Derivatives

As an important messenger and biotic activator, mononitrogen monoxide (NO) was believed involved the physiology activity, promotion angiogenesis, accommodation blood vessel- endothelium growth. NO donor in the body by the enzyme or non-enzymatic can be released NO. Recently, people in order to increase the activity of drugs, have begun to tend to the NO donor into the structure of drug molecules.With C6-C3-C6 as the fundamental structure, chrysin (5,7-dihydroxyflavone) is a naturally wide distributed flavonoid, which has been reported to have many different biological activities such as anti-viral, anti-cancer, anti-bactericidal, anti-flammatory, anti-allergic, DNA cleavage, vasodilator, anti-mutagenic, anti-anxiolytic and anti-oxidant effects. To get better therapeutic effect, much effort has been devoted to the modification and chemical synthesis of chrysin in recent years. However, the research on the role of chyrin and its derivatives in anti-diabetes and anti-diabetic vascular complications is still in its infant stage.Different chrysin derivatives were successfully coupled to NO donors and we hope this kind of compounds could act asα-Glucosidase Inhibition reagents and promotion angiogenesis reagents as well as anti-diabetes and anti-diabetic vascular complications. Using chrysin as the starting material, different NO donors were coupled to the active hydroxy group at the 7-position of chrysin and acetylation of hydroxy group at the 5-position could be occurred at the same time. Thus 16 new compounds (including 9 nitro ester compounds, 6 furazan derivatives and 1 N-hydroxy carbamidine compound) were prepared by similar method and all of them were characterized by means of 1H NMR and MS (EI).In vivoα-glucosidase inhibition, MTT cell proliferation and CAM angiogenesis experiments were performed to evaluate these compounds'activity. It was found that all of the 9 nitro ester compounds and 6 furazan compounds showedα-glucosidase inhibition activity, among them, 6 compounds'(7b, 17, 18, 15b, 15a, 16b) IC50 value are less than 20μmol/L, which is much better than the reference compound acarbose. All target compounds did not show any cytotoxicity in the MTT in vivo experiments under 10μmol/L concentration, however, 7a, 7b, 7c, 5a, 5b, 5c and 17 exhibited cell proliferation activity on HUVECs-12. In the meantime, among those 15 compounds investigated by CAM assay, 7a, 7b, 7c, 5a, 5b, 5c, 17, 15b, 15a, 16b and 16a showed strong angiogenic activities.These results indicated that these compounds we prepared have excellent angiogenic activity in vivo andα-glucosidase inhibition activity, among them compounds 7b, 17, 15b, 15a and 16b are the best and worth for further investigation for anti-diabetes and anti-diabetic vascular complications applications.