Resveratrol–Maltol and Resveratrol–Thiophene Hybrids as Cholinesterase Inhibitors and Antioxidants: Synthesis, Biometal Chelating Capability and Crystal Structure
| Autor: | Milena Mlakić, Lajos Fodor, Ilijana Odak, Ottó Horváth, Marija Jelena Lovrić, Danijela Barić, Valentina Milašinović, Krešimir Molčanov, Željko Marinić, Zlata Lasić, Irena Škorić |
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| Rok vydání: | 2022 |
| Předmět: |
Galantamine
Organic Chemistry Pharmaceutical Science Thiophenes Ligands Antioxidants Trace Elements Analytical Chemistry Molecular Docking Simulation Structure-Activity Relationship cholinesterase inhibitory activity molecular docking pyran-4-ones thienostilbenes Alzheimer Disease Pyrones Resveratrol Chemistry (miscellaneous) Drug Discovery Cholinesterases Humans Molecular Medicine Cholinesterase Inhibitors Physical and Theoretical Chemistry Chelating Agents |
| Zdroj: | Molecules; Volume 27; Issue 19; Pages: 6379 |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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