Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents
Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obt...
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/6/1781 |
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| author | Cynthia Sinyeue Mariko Matsui Michael Oelgemöller Frédérique Bregier Vincent Chaleix Vincent Sol Nicolas Lebouvier |
| author_facet | Cynthia Sinyeue Mariko Matsui Michael Oelgemöller Frédérique Bregier Vincent Chaleix Vincent Sol Nicolas Lebouvier |
| author_sort | Cynthia Sinyeue |
| collection | DOAJ |
| description | Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (<b>4G</b>), 2′-carboxy-5,7-dimethoxy-flavanone (<b>4F</b>), 4′-bromo-5,7-dimethoxy-flavanone (<b>4D</b>), and 2′-carboxyflavanone (<b>4J</b>), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC<sub>50</sub> value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the <i>meta</i>-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the <i>para</i>-position were less active. The addition of methoxy-groups in the <i>meta</i>-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents. |
| first_indexed | 2024-03-09T13:11:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:11:17Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-1602d151bc4f413a945e04f1bd8b2d9f2023-11-30T21:41:04ZengMDPI AGMolecules1420-30492022-03-01276178110.3390/molecules27061781Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory AgentsCynthia Sinyeue0Mariko Matsui1Michael Oelgemöller2Frédérique Bregier3Vincent Chaleix4Vincent Sol5Nicolas Lebouvier6Institut des Sciences Exactes et Appliquées (ISEA) EA7484, Campus de Nouville, Université de la Nouvelle Calédonie, Noumea 98851, New CaledoniaInstitut des Sciences Exactes et Appliquées (ISEA) EA7484, Campus de Nouville, Université de la Nouvelle Calédonie, Noumea 98851, New CaledoniaCollege of Science and Engineering, Discipline of Chemistry, James Cook University, Townsville, QLD 4811, AustraliaLaboratoire PEIREINE UR 22722, Faculté des Sciences et Techniques, 87060 Limoges, FranceLaboratoire PEIREINE UR 22722, Faculté des Sciences et Techniques, 87060 Limoges, FranceLaboratoire PEIREINE UR 22722, Faculté des Sciences et Techniques, 87060 Limoges, FranceInstitut des Sciences Exactes et Appliquées (ISEA) EA7484, Campus de Nouville, Université de la Nouvelle Calédonie, Noumea 98851, New CaledoniaFlavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (<b>4G</b>), 2′-carboxy-5,7-dimethoxy-flavanone (<b>4F</b>), 4′-bromo-5,7-dimethoxy-flavanone (<b>4D</b>), and 2′-carboxyflavanone (<b>4J</b>), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC<sub>50</sub> value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the <i>meta</i>-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the <i>para</i>-position were less active. The addition of methoxy-groups in the <i>meta</i>-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.https://www.mdpi.com/1420-3049/27/6/1781flavanoneanti-inflammatory activitystructure–activity relationship (SAR)RAW264.7pinocembrin |
| spellingShingle | Cynthia Sinyeue Mariko Matsui Michael Oelgemöller Frédérique Bregier Vincent Chaleix Vincent Sol Nicolas Lebouvier Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents Molecules flavanone anti-inflammatory activity structure–activity relationship (SAR) RAW264.7 pinocembrin |
| title | Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents |
| title_full | Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents |
| title_fullStr | Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents |
| title_full_unstemmed | Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents |
| title_short | Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents |
| title_sort | synthesis and investigation of flavanone derivatives as potential new anti inflammatory agents |
| topic | flavanone anti-inflammatory activity structure–activity relationship (SAR) RAW264.7 pinocembrin |
| url | https://www.mdpi.com/1420-3049/27/6/1781 |
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