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Design and Synthesis of Novel Double-Ring Conjugated Enones as Potent Anti-rheumatoid Arthritis Agents.


ABSTRACT: Rheumatoid arthritis (RA) is a chronic and systemic disease of inflammatory synovitis with unknown etiology. In previous studies, we found that the double-ring conjugated enone structure has anti-rheumatoid arthritis activity and could effectively inhibit the proliferation of rat synovial cells in vitro and has good anti-inflammatory activity in vivo. Herein, we further modified the structure, which was a novel double-ring conjugated enone, to study its anti-rheumatoid arthritis activity. Results showed that the most potent compound 32 could effectively inhibit the proliferation of rat synovial cells in vitro and has better anti-inflammatory activity compared with that of the positive control methotrexate, as shown by in vivo activity evaluation. More interestingly, compound 32 could effectively inhibit the increase of TNF-α, IL-1β, and IL-6 induced by LPS and regulate the expression of TLR4, MyD88, NF-κB, and IκB in the signaling pathway of TLR4/NF-κB. Our results provided a promising starting point for the development of highly effective small molecules for the treatment of RA.

SUBMITTER: Zhou S 

PROVIDER: S-EPMC9730744 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Design and Synthesis of Novel Double-Ring Conjugated Enones as Potent Anti-rheumatoid Arthritis Agents.

Zhou Shiyang S   Jiang Wenming W   Chen Guangying G   Huang Gangliang G  

ACS omega 20221117 48


Rheumatoid arthritis (RA) is a chronic and systemic disease of inflammatory synovitis with unknown etiology. In previous studies, we found that the double-ring conjugated enone structure has anti-rheumatoid arthritis activity and could effectively inhibit the proliferation of rat synovial cells <i>in vitro</i> and has good anti-inflammatory activity <i>in vivo</i>. Herein, we further modified the structure, which was a novel double-ring conjugated enone, to study its anti-rheumatoid arthritis ac  ...[more]

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