Synthesis Of Flavonoid Multi-target Derivatives On Diabetic Vascular Complications

Nowadays, diabetes mellitus is wide chronic disease, which would necessarilyaccompany with serious complication in the world, and belong to comprehensivedisease with metabolic disorders. In the present, vascular complication of diabetes ismain threat to people’s health because of its high fatality and disability rate.According to recent research, hyperglycemia is the primary element that resulted inmicroangiopathy. The abnormality of four metabolic pathways was main reason ofvascular complication, such as, the hypermetabolism of polyol pathway, increasing ofAGEs formation, activating of PKC, rising of HBP activity. According to that,single-target drug could not serves as effective control and treatment for complexpathogenesis of diabetes and its vascular complications. Hence, in order to ease andcure the diabetes and its vascular complications, the more comprehensivemulti-targets drug should be designed.The flavonoids is a familiar kind of natural compounds, which have lots ofpharmacology activities, such as, hypoglycemic effect, antioxidation, scavenging freeradical, anti-arteriosclerosis, anti-tumor. Alkyl and ester are linked with flavonoid toobtain a series of derivatives, they would possess some pharmacological activity, forexample, hpyerglycemic, antioxidant, anti-arteriosclerosis of vessel, which could beintensified.It is known that NO possessed many vital physiological effects, for example,diastolic blood vessels, scavenging free radical, promoting and repairing theendothelial progenitor cell, which could retard and treat the diabetes vascularcomplications. Therefore, the flavonoid could be applied to treat the diabetes and itscomplications with less side effects. If NO donor is coupled with flavonoids to obtainsome novel flavonoid derivatives, which may possess many activities, for example,hpyerglycemic, antioxidant and so on. On the other hand, NO could be released forscavenging free radical and accelerating the growing and repair of EPCs. In the end,those derivatives could be as multi-targets.In the study, we had design and synthesized15flavonoid alkyl derivatives,include6diosmetin alkyl derivatives, and3chrysin, apigenin, luteolin alkylderivatives, respectively;6diosmetin ester derivatives;12NO donor derivatives ofdiosmetin, and structures of all compounds were confirmed by1H NMR, MALDI-TOF, et al.All compounds displayed preferable pharmacological activities in vitro, such as,inhibition for formation of AGEs, α-glucosidase, aldose reductase, and scavengingABTs radicals. Moreover, NO-donor derivatives of diosmetin could release NO withcertain concentration. Therefore, these compounds could have a chance become novelmulti-targets drugs to treat diabetes and its vascular complications, and used asreferences for other researchers to design multi-targets.