Synthesis, biochemical characterization and computational investigations of newly synthesized crystal structure of Dihydropyrimidin-2(1H)-thione

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The novel 1-(2,6-dibromo-4-fluorophenyl)-4,4,6-trimethyl-3,4-dihydropyrimidine-2(1H)-thiones molecule has been synthesized through a convenient and simple protocol by the facile reaction of acetone, potassium thiocyanate and 2,6-dibromo-4-fluoroaniline. The structure of synthesized compound has been confirmed by spectroscopic (IR, 1H NMR, 13C NMR,), elemental and single crystal analyses. The x-ray studies exhibited the presence of two six-fold ring planes that are almost perpendicular with a dihedral angle of 89.84(7) °. The crystal studies employing Hirshfeld surface (HS) analysis revealed the presence of large number of H … H, H … Br/Br … H, H … S/S … H, H … F/F … H and H … C/C … H interactions suggesting the major role of van der Waals interactions and hydrogen bonding in the crystal packing. DFT studies were performed using the B3LYP function and 6-31G basis set to optimize the molecular geometry. Both in-vitro enzyme inhibition analysis and in-silico molecular docking studies were conducted to confirm the antidiabetic and anti-Alzheimer’s effects. The enzyme inhibition data demonstrated the potent inhibitory activity against acetylcholinesterase (65.5 ± 2.6 µM), butyryl cholinesterase (125.5 ± 2.0 µM) and α-glucosidase (156.0 ± 5.1 µM), while a lesser effect against α-amylase enzyme. These results were further confirmed by in-silico studies which showed strong binding interactions within the active site of target receptor proteins such as α-amylase, α-glucosidase, acetylcholinesterase and butyryl cholinesterase respectively. These findings highlight the potential of compound 4 as a therapeutic agent for the treatment of diabetes and Alzheimer’s disease.