2. Academic Validation
  3. Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells

Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells

  • Bioorg Chem. 2021 Feb;107:104630. doi: 10.1016/j.bioorg.2021.104630.
Soha H Emam 1,  Amr Sonousi 2,  Eman O Osman 1,  Dukhyun Hwang 3,  Gun-Do Kim 3,  Rasha A Hassan 1
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • 2 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt. Electronic address: amr.motawi@pharma.cu.edu.eg.
  • 3 Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 48513, Republic of Korea.
PMID: 33476864 DOI: 10.1016/j.bioorg.2021.104630
Abstract

Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based Chalcones 2a-l and coumarin-based Chalcones 3a-f were synthesized and compared for their inhibition of COX-2 Enzyme and nitric oxide production suppression. Methoxylated phenyl-based Chalcones showed better inhibition to COX-2 Enzyme and nitric oxide suppression than the coumarin-based Chalcones. Among the 18 synthesized chalcone derivatives, compound 2f exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC50 = 11.2 μM). The tested compound 2f showed suppression of iNOS and COX-2 Enzymes. Moreover, compound 2f decreases in the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKKβ as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.

Keywords

Anti-inflammatory; Chalcones; LPS-induced RAW264.7 macrophages; Molecular docking; Nitric oxide inhibition; Nuclear factor kappa B.

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