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

Journal Publication ResearchOnline@JCU
Sinyeue, Cynthia;Matsui, Mariko;Oelgemöller, Michael;Brégier, Frédérique;Chaleix, Vincent;Sol, Vincent;Lebouvier, Nicolas
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.

Journal

Molecules

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Volume

27

ISBN/ISSN

1420-3049

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Pages Count

19

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Publisher

MDPI

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N/A

DOI

10.3390/molecules27061781