In vitro and in Silico Antidiabetic studies of 5,7,8-Trihydroxyflavone

The search for safe and effective antidiabetic agents has continued to be an important area of investigation worldwide. Though flavonoids are one of the most abundant groups of secondary plant metabolites, the interest in flavonoids has only increased in the last years due to their hydrophilic nature and their relevant in vitro and in vivo pharmacological properties. In our research laboratory, 5,7,8-trihydroxyflavone (5,7,8-THF) isolated from the leaves extract of Tetracera indica Merr. has been observed to show an in vitro antidiabetic effect during preliminary investigations supporting it to be an antihyperglycemic agent that could improve insulin sensitivity, ameliorate metabolic lipid disorders, and benefit certain disorders characterized by insulin resistance. Hence, the present research will highlight the structural optimization of 5,7,8-THF to obtain the novel derivatives with enhanced effects on glucose metabolism. Different synthetic strategies were considered to synthesize its chemical analogues in our pursuit to obtain more efficacious flavonoid-based antidiabetic agent. In vitro antioxidant, α-glucosidase and DPP-4 inhibition results supported it to be a potential antidiabetic agent. In silico molecular docking study was conducted to understand its molecular interaction with established pharmacological targets and mechanisms of actions at the molecular level as an antihyperglycemic agent. The results suggest that 5,7,8-THF can be considered as promising candidate in the development of new antidiabetic lead compound. Moreover, the precise mechanism of action of 5,7,8-THF based novel derivants for their antihyperglycemic effect may provide a strong foundation for the clinical studies in human beings as a promising safe anti-diabetic drug