Synthesis and investigation of flavanone derivatives as potential new anti-inflammatory agents

Sinyeue, Cynthia, Matsui, Mariko, Oelgemöller, Michael, Brégier, Frédérique, Chaleix, Vincent, Sol, Vincent, and Lebouvier, Nicolas (2022) Synthesis and investigation of flavanone derivatives as potential new anti-inflammatory agents. Molecules, 27. 1781.

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Abstract

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 RAW264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 20-carboxy-5,7-dimethoxy-flavanone (4F), 40-bromo 5,7-dimethoxy-flavanone (4D), and 20-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 microg/mL, respectively. In comparison, pinocembrin achieved an IC50 value of 203.60 microg/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 meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-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.

Item ID: 72994
Item Type: Article (Research - C1)
ISSN: 1420-3049
Keywords: flavanone; anti-inflammatory activity; structure–activity relationship (SAR); RAW264.7; pinocembrin
Copyright Information: Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Date Deposited: 17 Mar 2022 01:01
FoR Codes: 34 CHEMICAL SCIENCES > 3405 Organic chemistry > 340502 Natural products and bioactive compounds @ 50%
34 CHEMICAL SCIENCES > 3405 Organic chemistry > 340503 Organic chemical synthesis @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280105 Expanding knowledge in the chemical sciences @ 100%
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