Discovery Potent of Thiazolidinedione Derivatives as Antioxidant, α-Amylase Inhibitor, and Antidiabetic Agent.

This work aimed to synthesize safe antihyperglycemic derivatives bearing thiazolidinedione fragment based on spectral data. The DFT theory discussed the frontier molecular orbitals (FMOs), chemical reactivity of compounds, and molecular electrostatic potential (MEP) to explain interaction between thiazolidinediones and the biological receptor. α-amylase is known as the initiator-hydrolysis of the of polysaccharides; therefore, developing α-amylase inhibitors can open the way for a potential diabetes mellitus drug. The molecular docking simulation was performed into the active site of PPAR-γ and α-amylase. We evaluated in vitro α-amylase's potency and radical scavenging ability. The compound 6 has the highest potency against α-amylase and radical scavenging compared to the reference drug and other members. They have been applied against anti-diabetic and anti-hyperlipidemic activity (in vivo) based on an alloxan-induced diabetic rat model during a 30-day treatment protocol. The most potent anti hyperglycemic members are 6 and 11 with reduction percentage of blood glucose level by 69.55% and 66.95%, respectively; compared with the normal control. Other members exhibited moderate to low anti-diabetic potency. All compounds showed a normal value against the tested biochemical parameters (CH, LDL, and HDL). The ADMET profile showed good oral bioavailability without any observed carcinogenesis effect.