An in vitro study of the 5-methyl- and 5-bromo/chloro substituted 2-hydroxy-3-nitrochalcones as α-glucosidase and/or α-amylase inhibitors with potential anti-inflammatory activity
Abstract Series of the 5-methyl-, 5-bromo- and 5-chloro substituted 2-hydroxy-3-nitrochalcones (2a–d), (2e–h) and (2i–l), respectively, have been synthesized and characterized using a combination of spectroscopic and single crystal X-ray diffraction techniques. The compounds were, in turn, evaluated through enzymatic assays in vitro for inhibitory effect against α-glucosidase and α-amylase activities. Most of the test compounds exhibited increased inhibitory activity against α-glucosidase compared to the anti-diabetic drug, acarbose. Chalcones 2a, 2c, 2d, and 2g–j exhibited dual inhibitory effect against both enzymes with minimal cytotoxicity against the Raw-264,7 macrophage (Murine) cells compared to the anticancer drug, curcumin. Derivatives 2e and 2k exhibited increased inhibitory activity and selectivity against α-amylase with significantly reduced cytotoxicity against the Raw-264,7 cells. Chalcones 2a, 2i, and 2j showed the capability to increase the phagocytic ability of Raw-264,7 cells in the presence of lipopolysaccharide (LPS) stimuli. Molecular docking has been performed on the most active derivatives to predict the hypothetical protein–ligand binding modes into the α-glucosidase and α-amylase binding sites. Selected compounds were also docked into the Toll-like receptor-myeloid differentiation factor 2 (TLR4-MD2) active sites to determine their binding energies at least at theoretical level. The key aspects of the pharmacokinetics of these compounds, namely, absorption, distribution, metabolism, and excretion have also been simulated..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Medicinal chemistry research - 31(2022), 12 vom: 27. Okt., Seite 2243-2259 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mphahlele, Malose J. [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s00044-022-02980-1 |
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| Förderinstitution / Projekttitel: |
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OLC2079883879 |
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| 520 | |a Abstract Series of the 5-methyl-, 5-bromo- and 5-chloro substituted 2-hydroxy-3-nitrochalcones (2a–d), (2e–h) and (2i–l), respectively, have been synthesized and characterized using a combination of spectroscopic and single crystal X-ray diffraction techniques. The compounds were, in turn, evaluated through enzymatic assays in vitro for inhibitory effect against α-glucosidase and α-amylase activities. Most of the test compounds exhibited increased inhibitory activity against α-glucosidase compared to the anti-diabetic drug, acarbose. Chalcones 2a, 2c, 2d, and 2g–j exhibited dual inhibitory effect against both enzymes with minimal cytotoxicity against the Raw-264,7 macrophage (Murine) cells compared to the anticancer drug, curcumin. Derivatives 2e and 2k exhibited increased inhibitory activity and selectivity against α-amylase with significantly reduced cytotoxicity against the Raw-264,7 cells. Chalcones 2a, 2i, and 2j showed the capability to increase the phagocytic ability of Raw-264,7 cells in the presence of lipopolysaccharide (LPS) stimuli. Molecular docking has been performed on the most active derivatives to predict the hypothetical protein–ligand binding modes into the α-glucosidase and α-amylase binding sites. Selected compounds were also docked into the Toll-like receptor-myeloid differentiation factor 2 (TLR4-MD2) active sites to determine their binding energies at least at theoretical level. The key aspects of the pharmacokinetics of these compounds, namely, absorption, distribution, metabolism, and excretion have also been simulated. | ||
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| 650 | 4 | |a α-amylase | |
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| 700 | 1 | |a Choong, Yee Siew |4 aut | |
| 700 | 1 | |a Monchusi, Bernice A. |4 aut | |
| 700 | 1 | |a Mbazima, Vusi G. |4 aut | |
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