Synthesis And Characterization Of Novel Of 1, 3, 4-Thiadiazole Derivatives As Potential Α-Amylase Inhibitor

Abstract

Background: 1,3,4-Thiadiazole derivatives have garnered interest due to their wide range of pharmacological activities, including potential as α-amylase inhibitors for managing diabetes. This study aimed to synthesize novel 1,3,4-thiadiazole derivatives, evaluate their in-vitro α-amylase inhibitory activity, and analyze their pharmacokinetic and drug-likeness properties. Methods: The derivatives were synthesized via a multi-step process involving the reaction of thiosemicarbazide with various substituted anilines and formaldehyde, followed by condensation with 4H-chromen-3-carbaldehyde. The synthesized compounds were characterized by FTIR, ¹H NMR, and melting point analysis. Molecular docking studies were performed to assess binding affinity with α-amylase, while in-vitro α-amylase inhibitory activity was evaluated using various concentrations (10-100 µg/mL). Pharmacokinetic properties and in-silico toxicity were analyzed for drug-likeness assessment. Results: All synthesized compounds showed moderate to high yields (67-93%) and were confirmed by spectral data. Molecular docking indicated that compound A8 had the strongest binding affinity with a docking score of -9.5 kcal/mol. In-vitro α-amylase inhibition studies revealed that A8 exhibited the highest inhibitory activity with an IC50 value of 44.67 µg/mL, surpassing the standard Acarbose (IC50: 60.51 µg/mL). Most compounds displayed favorable pharmacokinetic properties, including high gastrointestinal absorption and minimal blood-brain barrier permeation. Conclusion: The novel 1,3,4-thiadiazole derivatives, particularly A8, demonstrated significant potential as α-amylase inhibitors, showing strong binding affinity, effective enzyme inhibition, and promising pharmacokinetic profiles. These findings suggest that A8 could serve as a lead compound for further development in diabetes treatment.