Resveratrol–Maltol and Resveratrol–Thiophene Hybrids as Cholinesterase Inhibitors and Antioxidants: Synthesis, Biometal Chelating Capability and Crystal Structure

Mlakić, Milena; Fodor, Lajos; Odak, Ilijana; Horváth, Ottó; Lovrić, Marija Jelena; Barić, Danijela; Milašinović, Valentina; Molčanov, Krešimir; Marinić, Željko; Lasić, Zlata; Škorić, Irena (2022) Resveratrol–Maltol and Resveratrol–Thiophene Hybrids as Cholinesterase Inhibitors and Antioxidants: Synthesis, Biometal Chelating Capability and Crystal Structure. Molecules, 27 (19). ISSN 1420-3049

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Abstract

New resveratrol–thiophene and resveratrol–maltol hybrids were synthesized as cholinesterase inhibitors and antioxidants. As with photostability experiments, biological tests also found remarkable differences in the properties and behavior of thiophene and maltol hybrids. While resveratrol–thiophene hybrids have excellent inhibitory and antioxidant properties (similar to the activity of reference drug galantamine), maltols have been proven to be weaker inhibitors and antioxidants. The molecular docking of selected active ligands gave insight into the structures of docked enzymes. It enabled the identification of interactions between the ligand and the active site of both cholinesterases. The maltols that proved to be active cholinesterase inhibitors were able to coordinate Fe3+ ion, forming complexes of 1:1 composition. Their formation constants, determined by spectrophotometry, are very similar, lgK = 11.6–12.6, suggesting that Fe3+ binds to the common hydroxy-pyranone moiety and is hardly affected by the other aromatic part of the ligand. Accordingly, the characteristic bands in their individual absorption spectra are uniformly red-shifted relative to those of the free ligands. The crystal structures of two new resveratrol–maltol hybrids were recorded, giving additional information on the molecules’ intermolecular hydrogen bonds and packing. In this way, several functionalities of these new resveratrol hybrids were examined as a necessary approach to finding more effective drugs for complicated neurodegenerative diseases.

Item Type:	Article
Uncontrolled Keywords:	cholinesterase inhibitory activity; molecular docking; pyran-4-ones; thienostilbenes
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Physical Chemistry NMR Center
Depositing User:	Diana Mikoč Radešić
Date Deposited:	31 Jan 2024 08:43
URI:	http://fulir.irb.hr/id/eprint/8424
DOI:	10.3390/molecules27196379

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