Development of Novel α-Amylase Inhibitors: Synthesis, Molecular Docking, and Biochemical Studies

The rising prevalence of diabetes as a major non-communicable disease underscores the critical need for effective anti-diabetic agents. The new analogs designed 3a-3j were effectively synthesised and thoroughly characterised using (¹H, ¹³C NMR, FT-IR, GCMS, and HRMS) to investigate their structural biochemical properties. The novel analogs were investigated thoroughly by in silico (molecular docking) and in vitro (anti-oxidant (DPPH, ABTS) activity, anti-inflammation (RBC), modifications of LDL and HDL, thiobarbituric substances, cholesterol efflux assay, and anti-diabetic) assays, validated for α-amylase inhibition. Enzyme inhibition results showed α-amylase IC₅₀ values of 1.79 ± 0.12 μg for compound 3d, 1.75 ± 0.05 μg for compound 3e, and 1.53 ± 0.20 μg for the standard drug acarbose. Among the new molecules, compounds 3c and 3d exhibited the highest inhibitory activity in all performed in silico and in vitro studies. The study demonstrated that inhibitors 3a-3j bind strongly to the active site of human pancreatic α-amylase, highlighting their potential as effective inhibitors. These research findings help to improve the field of developing lead molecules for anti-diabetic agents.