{
  "abstract": "Acute lung injury (ALI), characterized by dysregulated inflammation and oxidative stress, remains a major therapeutic challenge due to limited treatment options. Inspired by the anti-inflammatory activity of the in-house synthetic intermediate A1 , we designed and synthesized a series of chalcone derivatives through structural optimization, preserving the phenylthioether moiety while modifying the aromatic ring on one side of the chalcone olefin. Among these, compound B15 emerged as the lead candidate, exhibiting potent nitric oxide (NO) inhibition (IC 50 = 2.6 ± 1.4 μM) in LPS-stimulated RAW264.7 macrophages with minimal cytotoxicity (GI 50 > 100 μM). Mechanistic studies demonstrated that B15 directly binds to p38 MAPK with a K D value of 372.1 nM. It suppressed LPS-induced inflammatory responses in a concentration-dependent manner, downregulating TNF-α and IL-6 transcription, reducing intracellular ROS levels, and inhibiting the activation of multiple inflammatory-related MAPK cascades. In an LPS-induced murine model of ALI, B15 significantly attenuated pathological damage and inflammatory response, including alveolar collapse, interstitial edema, and neutrophil infiltration. Collectively, these finding establish B15 as a promising anti-inflammatory lead for ALI therapy via p38 MAPK inhibition, meriting further pharmacological development.",
  "abstract_shown": true,
  "affiliations": [
    "Anhui Province Key Laboratory of Inflammation and Immune Diseases, The Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, School of Pharmacy, Anhui Medical University, Hefei, Anhui Province, 230032, PR China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qin-Li Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xue-Jian Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhao-Feng Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia-Xing Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin-Hua Liu"
    },
    {
      "name": "Ming-Ming Liu"
    },
    {
      "name": "Jing-Bo Shi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fggr2cx5ss470.bib",
  "cited_by": 0,
  "doi": "10.1016/j.rechem.2026.103976",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2211715626009501",
  "id": "fggr2cx5ss470",
  "issns": [
    "2211-7156"
  ],
  "landing_url": "https://doi.org/10.1016/j.rechem.2026.103976",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QD1-999"
    ],
    [
      "openalex",
      "1312|Bioactive natural compounds"
    ]
  ],
  "openalex": "W7221662735",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fggr2cx5ss470.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:51Z",
      "native_id": "23a3e4c77f2942409aa6857237cb2a4e",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.rechem.2026.103976"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bioactive natural compounds",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Phenylthioether chalcone derivatives attenuate acute lung injury via suppression of p38 MAPK (MAPK14)-mediated inflammatory signaling",
  "title_text": "Phenylthioether chalcone derivatives attenuate acute lung injury via suppression of p38 MAPK (MAPK14)-mediated inflammatory signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:51Z",
  "url": "https://research.draconitic.com/paper/fggr2cx5ss470",
  "venue": "Results in Chemistry",
  "versions": []
}