An ultrasound-assisted synthesis of novel Thiazole-pyrimidine hybrids: in-vitro PPA enzyme inhibition, DFT analysis, Molecular docking, MD simulation

This study gives structural information about the novel thiazole-pyrimidine hybrids ( P1 to P15 ). The compounds were synthesized and yield optimized by sonochemistry, characterized using various spectroscopic techniques, including mass, ¹ H-NMR, ¹³ C-NMR, and IR spectroscopy. The compounds were theoretically explored using the DFT approach with a B3LYP/6-311G (d, p) basis set, and their in vitro porcine pancreatic α-amylase (PPA) enzyme screening was done. Compared to the standard acarbose (IC ₅₀ = 0.34 mM), novel thiazole-pyrimidine hybrids ( P1 to P15 ) demonstrated porcine pancreatic α-amylase inhibition ranging from IC ₅₀ (0.33 to 0.73 mM). Molecular docking, MD simulation investigations, and ADMET were carried out to identify the active sites and explain the actions of the active substances by in silico molecular docking. The three active compounds P3 (IC ₅₀ 0.33 mM, -10.6 kcal/mol ), P2 (IC ₅₀ 0.37 mM, -10.5 kcal/mol), and P6 (IC ₅₀ 0.39 mM, -10.5 kcal/mol) were redocked at the active site of pig pancreatic alpha-amylase isoenzyme II (PDB ID: 1OSE ) to study the binding conformation and dynamics relevant to their activity. The binding interactions between P2, P3, and P6 with porcine pancreatic α-amylase showed porcine pancreatic α-amylase's inhibitory potential.