Discovery of Novel 1,3,5-triazine Derivatives As an Antidiabetic Agent in Wistar Rats Via Inhibition of DPP-4

Abstract

Aim: To develop imeglimin-inspired novel 1,3,5-triazine derivatives as antidiabetic agents. Materials & methods: These derivatives were synthesized and tested against DPP enzymes. Compound 8c was tested for in vivo antidiabetic activity in streptozotocin-induced diabetes in Wistar rats by estimating various biochemical parameters. Docking experiments were also performed. Results: Compound 8c was identified as a selective and potent DPP-4 inhibitor. It was proficiently docked into the catalytic triad of Ser 630, Asp 710 and His740 in S1 and S2 pockets of DPP-4. In experimental animals, it also showed dose-dependent improvement in blood glucose, blood insulin, bodyweight, lipid profile and kidney and liver antioxidant profiles. Conclusion: This study demonstrated the discovery of imeglimin-inspired novel 1,3,5-triazines as a potent antidiabetic agent.

Discovery of imeglimin-inspired novel 1,3,5-triazine derivatives as antidiabetic agents in streptozotocin-induced diabetes in Wistar rats via inhibition of DPP-4

“…All assay concepts, guidelines, and procedures were adhered to throughout the process by the manufacturer’s instructions. 47 After additional dilutions, test chemical concentrations (25, 50, and 100 μg mL −1 ) were prepared with DMSO and applied to each well. These were incubated at 37 °C for 10 min to allow for the enzyme–inhibitor reaction, and they were continuously monitored at 405 nm using a plate reader (Bio-Rad, USA).…”

“…DPPH scavenging and hydrogen peroxide scavenging tests were performed as per the reported procedure to measure the antioxidant activity of compound 8c . 47…”

“…All assay concepts, guidelines, and procedures were adhered to throughout the process by the manufacturer's instructions. 47…”

“…DPPH scavenging and hydrogen peroxide scavenging tests were performed as per the reported procedure to measure the antioxidant activity of compound 8c. 47 DPPH scavenging activity. Following the addition of 2 ml of a 0.5 mM DPPH solution, 0.2 ml of compound 8c at various concentrations (25,50, and 100 μg mL −1 ) was diluted with methanol.…”

Dexmedetomidine attenuates myocardial ischemia–reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF‐κB

“…The serum levels of various lipid biomarkers total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very lowdensity lipoprotein (VLDL) were estimated using the previously described procedure (Gupta et al, 2023a;Gupta et al, 2023b).…”