Synthesis and in vitro and in vivo anti-inflammatory activity of novel 4-ferrocenylchroman-2-one derivatives

Wei-Yun Guo,Liu-Zeng Chen,Bang-Nian Shen,Xin-Hua Liu,Guang-Ping Tai,Qing-Shan Li,Li Gao,Ban-Feng Ruan

doi:10.1080/14756366.2019.1664499

Abstract

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.

Highlights

Rheumatoid arthritis (RA), which affects about 1% of the population worldwide, is a chronic systemic inflammatory disease characterised by inflammation and progressive joint destruction1,2
The clinical therapies to date mainly focused on nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and biological products like TNF-a antibody infliximab, the soluble TNF-a receptor etanercept, and interleukin1 (IL-1)-receptor antagonist anakinra3,4
We reported a resveratrol-based cinnamic ester hybridbenzo[d] [1,3] dioxol-5-yl (E)-3-(2,4-dimethoxy-6-((E)-4methoxystyryl) phenyl) acrylate (A, Figure 1), this compound exhibited potent inhibitory effect against LPS-stimulated Nitric oxide (NO) production as well as the expressions of inducible nitric oxide synthase (iNOS) and COX-2 in RAW 264.7 cells7

Summary

Introduction

Rheumatoid arthritis (RA), which affects about 1% of the population worldwide, is a chronic systemic inflammatory disease characterised by inflammation and progressive joint destruction. We reported a resveratrol-based cinnamic ester hybridbenzo[d] [1,3] dioxol-5-yl (E)-3-(2,4-dimethoxy-6-((E)-4methoxystyryl) phenyl) acrylate (A, Figure 1), this compound exhibited potent inhibitory effect against LPS-stimulated NO production as well as the expressions of iNOS and COX-2 in RAW 264.7 cells. We reported a resveratrol-based cinnamic ester hybridbenzo[d] [1,3] dioxol-5-yl (E)-3-(2,4-dimethoxy-6-((E)-4methoxystyryl) phenyl) acrylate (A, Figure 1), this compound exhibited potent inhibitory effect against LPS-stimulated NO production as well as the expressions of iNOS and COX-2 in RAW 264.7 cells7 This compound could exert the antiinflammatory activity partly due to its inhibitory effect on the NFjB signalling pathway. We preliminarily evaluated their anti-inflammatory activities by evaluating their inhibitory effects against LPS-stimulated NO, IL-6, and TNF-a production in RAW 264.7 cells. Compound 3h was selected to carry out further in vitro and in vivo evaluations for exploration of the possible anti-inflammatory mechanisms

Materials and methods

Results and discussion

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