Discovery Potent of Thiazolidinedione Derivatives as Antioxidant, α-Amylase Inhibitor, and Antidiabetic Agent
Manal Y. Sameeha✉, Manal M. Khowdiarya b, Hisham S. Nassarc d, Mahmoud Mohamed Abdelallc, Suliman ahmed Alderhamid, Ahmed A. Elhenawyc d✉
- aChemistry Department, Faculty of Applied Science, Alleeth University Collage, Umm Al-Qura University, Makkah 24211, Saudi Arabia
- bApplied Surfactant Laboratory, Egyptian Petroleum Research Institute, Nasr City 11727, Cairo, Egypt
- cChemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt
- dDepartment of Chemistry, Faculty of Science and Arts in Al-Mukhwah, Al-Baha University, Al-Mukhwah 65311, Saudi Arabia
- ✉Corresponding author
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
Abstract
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.
TL;DRThe most potent anti hyperglycemic derivatives bearing thiazolidinedione fragment are 6 and 11, which 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. (Semantic Scholar)