Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacology
2.3. Computer-Aided Studies Using an Internal Database of Coumarins and Chromone Analogs
2.3.1. D-QSAR Studies
Steric Map of MAO-B Inhibitors
Electrostatic Map of MAO-B Inhibitors
Hydrophobic Map of MAO-B Inhibitors
Hydrogen-Bond Donor Map of MAO-B Inhibitors
2.3.2. Molecular Docking
2.4. Computational Studies for the New Coumarin-Resveratrol-Inspired Hybrids
3. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compounds | IC50 hMAO-A (µM) | IC50 hMAO-B (µM) | S.I. * |
---|---|---|---|
3-Phenylcoumarin | >100 | 11.81 | >8.47 |
trans-6-Styrylcoumarin | >100 | 0.110 | >909.09 |
trans-Resveratrol | 17.41 | 29.37 | 0.59 |
Selegiline | 67.25 | 0.020 | 3362.5 |
Iproniazid | 6.56 | 7.54 | 0.87 |
Compounds | pIC50 MAO-A | ||||
---|---|---|---|---|---|
Exp. | CoMFA | Res | CoMSIA | Res | |
3-Phenylcoumarin | <4.000 | - | - | - | - |
trans-6-Styrylcoumarin | <4.000 | - | - | - | - |
trans-Resveratrol | 4.759 | 4.767 | 0.008 | 4.759 | −0.008 |
Compounds | pIC50 MAO-B | ||||
---|---|---|---|---|---|
Exp. | CoMFA | Res | CoMSIA | Res | |
3-Phenylcoumarin | 4.928 | 5.309 | −0.381 | 5.700 | −0.772 |
trans-6-Styrylcoumarin | 6.959 | 7.212 | −0.254 | 7.000 | −0.041 |
trans-Resveratrol | 4.532 | 5.173 | −0.641 | 5.362 | −0.830 |
Parameters (Energy) | Enzyme-Ligand Complexes | |||
---|---|---|---|---|
MAO-B and 3-phenylcoumarin (kJ/mol) | MAO-B and 3-(3′-bromophenyl)-6-Methylcoumarin (kJ/mol) | MAO-B and trans-6-styrylcoumarin (kJ/mol) | MAO-B and trans-resveratrol (kJ/mol) | |
Van der Waals | −145.335 ± 6.596 | −137.996 ± 8.218 | −152.618 ± 9.322 | −178.535 ± 8.654 |
Electrostatic | −2.253 ± 4.536 | −4.754 ± 7.797 | −31.762 ± 4.914 | 0.826 ± 4.532 |
Polar solvation | 99.294 ± 7.536 | 133.773 ± 19.676 | 137.238 ± 8.533 | 94.308 ± 7.084 |
SASA | −13.845 ± 0.623 | −17.202 ± 0.826 | −14.723 ± 0.709 | −15.502 ± 0.767 |
Binding free | −62.139 ± 9.680 | −26.179 ± 16.851 | −61.865 ± 10.412 | −98.903 ± 9.527 |
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Mellado, M.; González, C.; Mella, J.; Aguilar, L.F.; Celik, I.; Borges, F.; Uriarte, E.; Delogu, G.; Viña, D.; Matos, M.J. Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin. Molecules 2022, 27, 928. https://doi.org/10.3390/molecules27030928
Mellado M, González C, Mella J, Aguilar LF, Celik I, Borges F, Uriarte E, Delogu G, Viña D, Matos MJ. Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin. Molecules. 2022; 27(3):928. https://doi.org/10.3390/molecules27030928
Chicago/Turabian StyleMellado, Marco, César González, Jaime Mella, Luis F. Aguilar, Ismail Celik, Fernanda Borges, Eugenio Uriarte, Giovanna Delogu, Dolores Viña, and Maria J. Matos. 2022. "Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin" Molecules 27, no. 3: 928. https://doi.org/10.3390/molecules27030928