Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues.

Abstract

Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.

• Authors: Wenxi Wu, Yu Mu, Bo Liu, Zixuan Wang, Peipei Guan, Li Han, Mingguo Jiang, Xueshi Huang
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 111 Pg. 104898 (06 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 33894428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclotides
• Lipopolysaccharides
• NF-kappa B
• violacin A
• Nitric Oxide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, chemistry, pharmacology)
• Biomimetic Materials (chemical synthesis, chemistry, pharmacology)
• Cyclotides (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Mice
• Molecular Structure
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide (antagonists & inhibitors, metabolism)
• RAW 264.7 Cells
• Structure-Activity Relationship