{
  "abstract": "Obesity and its cardiometabolic complications remain a major public-health burden. Leptin resistance is a common feature of hyperleptinemic obesity, but the molecular basis of leptin resensitization remains incompletely understood, making the rational optimization of leptin-sensitizing agents difficult. Withaferin A (1) has been reported to enhance leptin responsiveness and to reduce body weight and the fasting blood glucose in diet-induced obese (DIO) mice. In this study, a series of withaferin A derivatives (2–15) bearing modifications in the A/B-ring region and the C-27 side-chain/lactone moiety was synthesized and evaluated in DIO mice. The compounds were administered intraperitoneally at 1.2 mg kg−1 once daily for 21 days. Withaferin A produced sustained reductions in body weight, cumulative food intake, and fasting blood glucose. Most derivatives showed weaker or less consistent responses, although compounds 2, 6, 10, and 12 significantly reduced body weight relative to the vehicle group at day 21. Overall, withaferin A (1) showed the most consistent response across the measured endpoints. These results suggest that structural modifications in either the A/B-ring region or the C-27 side-chain/lactone moiety affect the in vivo phenotypic responses of withaferin A. This study provides preliminary phenotype-level in vivo SAR information for withaferin A derivatives and may assist the design of compounds for further evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Pharmaceutical College, Guangxi Medical University Nanning 530021 Guangxi PR China",
    "Department of Research & Clinical Laboratory, Department of Administrative Office, The Fifth Affiliated Hospital of Guangxi Medical University, The First People's Hospital of Nanning Nanning 530022 Guangxi PR China",
    "Department of Oncology, Affiliated Hospital of YouJiang Medical University For Nationalities, Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Guangxi Higher Education Engineering Research Center for Gastrointestinal Microecology and Health, Baise City Key Laboratory of Gastrointestinal Microecology and Health Baise 533000 Guangxi PR China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhiming Yan",
      "orcid": "0009-0001-2030-9203"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingming Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyi Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Changhong Wei"
    },
    {
      "affs": [
        2
      ],
      "name": "Yiheng Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Hongyu Li",
      "orcid": "0009-0000-0180-5159"
    },
    {
      "affs": [
        2
      ],
      "name": "Tingzhuang Yi"
    },
    {
      "affs": [
        1
      ],
      "name": "Shixiong Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fqcz2et54258p.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra01511e",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13650539/",
  "id": "fqcz2et54258p",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://doi.org/10.1039/d6ra01511e",
  "language": "en",
  "licence": "CC-BY-3.0",
  "licence_label": "CC BY 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "2707|Phytochemicals and Medicinal Plants"
    ]
  ],
  "openalex": "W7221159217",
  "pdf_url": "https://pubs.rsc.org/ra/article-pdf/doi/10.1039/d6ra01511e/14864410/d6ra01511e.pdf",
  "pmcid": "PMC13650539",
  "pmid": "42857375",
  "published": "2026-10-09",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/fqcz2et54258p.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:34Z",
      "native_id": "PMC13650539",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra01511e"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "heading:Chemistry",
      "subfield": "general"
    }
  ],
  "title": "Synthesis of withaferin a derivatives and exploratory evaluation of weight reduction and fasting blood glucose in DIO mice",
  "title_text": "Synthesis of withaferin a derivatives and exploratory evaluation of weight reduction and fasting blood glucose in DIO mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:20:48Z",
  "url": "https://research.draconitic.com/paper/fqcz2et54258p",
  "venue": "RSC Advances",
  "versions": []
}