Synthesis of new sulfamate linked 4-hydroxycoumarin conjugates as potent anti-α-amylase agents: In vitro approach coupled with molecular docking, DFT calculation and chemoinformatics prediction

This work describes the design and synthesis of new coumarin-sulfamate derivatives by the action of a series of aliphatic alcohols on (4-hydroxycoumarine-3-carbonyl)sulfamoyl chloride 2 , previously prepared by reacting 4-hydroxycoumarine 1 with chlorosulfonyl isocyanate. Different spectroscopic techniques ( 1 H NMR, 13 C NMR and ESI-HRMS) were used to confirm their chemical structures. The prepared compounds were tested as alpha-amylase inhibitors in preliminary biological studies. The majority of compounds, espe-cially 3a, 3e, 3f and 3 h showed good ability to inhibit alpha-amylase enzyme (IC50 = 0.52-6.01 mu g/mL). All the synthesized compounds were theoretically studied using the Density Functional Theory (DFT) method with a B3LYP-D3(BJ)/6-311 ++ G(d,p) basis set to determine structural and some spectroscopic parameters with the HyperChem 8.03 software. Furthermore, they were docked into an alpha-amylase active site. The strength of intermolecular hydrogen bonding and hydrophobic interactions in ligand-receptor complexes were found to be significant descriptors in explaining the inhibition results. The pharmacokinetic pro-file of the synthesized derivatives was also predicted. The physicochemical properties determined were found to be within the desired range, and their agreement with Lipinski's rule of five, shows that most compounds are likely to be orally active. The significant results obtained with some of the newly syn-thesized compounds encourage in vivo anti-alpha-amylase research in order to reach promising antidiabetic candidates.(c) 2022 Elsevier B.V. All rights reserved.