Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2Y14R antagonists with potential high efficiency against acute gouty arthritis

Lu, Ran; Wang, Yilin; Liu, Chunxiao; Zhang, Zhenguo; Li, Baiyang; Meng, Zhaoqing; Jiang, Cheng; Hu, Qinghua

doi:10.1016/j.ejmech.2021.113313

Cited by 16 publications

(24 citation statements)

References 29 publications

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“…Moreover, it exerted promising in vivo efficacy in alleviating paw swelling and inflammatory infiltration in monosodium urate-induced acute gouty arthritis mice model. Elucidation of the preliminary mechanism of compound 91 indicated that it blocked pyroptosis of macrophages through inhibiting activation of NLRP3 inflammasome 106 .…”

Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 99%

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Bian

Wu³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Inflammation and disease are closely related. Inflammation can induce various diseases, and diseases can promote inflammatory response, and two possibly induces each other in a bidirectional loop. Inflammation is usually treated using synthetic anti-inflammatory drugs which are associated with several adverse effects hence are not safe for long-term use. Therefore, there is need for anti-inflammatory drugs which are not only effective but also safe. Several researchers have devoted to the research and development of effective anti-inflammatory drugs with little or no side effects. In this review, we studied some small molecules with reported anti-inflammatory activities and hence potential sources of anti-inflammatory agents. The information was retrieved from relevant studies published between January 2019 and May, 2021 for review. This review study was aimed to provide relevant information towards the design and development of effective and safe anti-inflammation agents.

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Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 99%

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Bian

Wu³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Currently, attempts are made to use targeted purinergic receptor therapy in gout. In a recent study, researchers designed and synthesized a novel P2Y 14 receptor antagonist, which reduced the MSU-induced joint swelling and inflammatory infiltration in an acute gouty arthritis mouse model ( 87 , 88 ), thus, improving the clinical value of targeted purinergic signaling in gout. However, the regulation of inflammation by purinergic signaling is much more complex than expected.…”

Section: Discussionmentioning

confidence: 99%

Purinergic Signaling in the Regulation of Gout Flare and Resolution

Gao

Tao

2021

Front. Immunol.

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Gout flares require monosodium urate (MSU) to activate the NLRP3 inflammasome and secrete sufficient IL-1β. However, MSU alone is not sufficient to cause a flare. This is supported by the evidence that most patients with hyperuricemia do not develop gout throughout their lives. Recent studies have shown that, besides MSU, various purine metabolites, including adenosine triphosphate, adenosine diphosphate, and adenosine bind to different purine receptors for regulating IL-1β secretion implicated in the pathogenesis of gout flares. Purine metabolites such as adenosine triphosphate mainly activate the NLRP3 inflammasome through P2X ion channel receptors, which stimulates IL-1β secretion and induces gout flares, while some purine metabolites such as adenosine diphosphate and adenosine mainly act on the G protein-coupled receptors exerting pro-inflammatory or anti-inflammatory effects to regulate the onset and resolution of a gout flare. Given that the purine signaling pathway exerts different regulatory effects on inflammation and that, during the inflammatory process of a gout flare, an altered expression of purine metabolites and their receptors was observed in response to the changes in the internal environment. Thus, the purine signaling pathway is involved in regulating gout flare and resolution. This study was conducted to review and elucidate the role of various purine metabolites and purinergic receptors during the process.

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“…In addition, NLRP3 interacts with cAMP to promote gout flare. The adenylate cyclase activator (forskolin) also causes pyroptosis [ 44 , 45 ]. Based on these findings, P2Y14R antagonists are expected to inhibit the occurrence of pyroptosis and relieve acute gouty arthritis [ 46 ].…”

Section: Introduction To Programmed Cell Death and Pyroptosismentioning

confidence: 99%

Cell pyroptosis in health and inflammatory diseases

Zhang

et al. 2022

Cell Death Discov.

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Inflammation is a defense mechanism that can protect the host against microbe invasion. A proper inflammatory response can maintain homeostasis, but continuous inflammation can cause many chronic inflammatory diseases. To properly treat inflammatory disorders, the molecular mechanisms underlying the development of inflammation need to be fully elucidated. Pyroptosis is an inflammation-related cell death program, that is different from other types of cell death. Pyroptosis plays crucial roles in host defense against infections through the release of proinflammatory cytokines and cell lysis. Accumulating evidence indicates that pyroptosis is associated with inflammatory diseases, such as arthritis, pneumonia, and colonitis. Furthermore, pyroptosis is also closely involved in cancers that develop as a result of inflammation, such as liver cancer, esophageal cancer, pancreatic cancer, and colon cancer. Here, we review the function and mechanism of pyroptosis in inflammatory disease development and provide a comprehensive description of the potential role of pyroptosis in inflammatory diseases.

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Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2Y14R antagonists with potential high efficiency against acute gouty arthritis

Cited by 16 publications

References 29 publications

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Purinergic Signaling in the Regulation of Gout Flare and Resolution

Cell pyroptosis in health and inflammatory diseases

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