2. Academic Validation
  3. Discovery of citrinin derivatives with SIRT1 agonist activity from Penicillium citrinum TJ507

Discovery of citrinin derivatives with SIRT1 agonist activity from Penicillium citrinum TJ507

  • Bioorg Chem. 2026 Mar:170:109473. doi: 10.1016/j.bioorg.2026.109473.
Yeting Zhang 1,  Xinye Huang 1,  Jiangchun Wei 2,  Jiajun Zhou 1,  Ming Chen 1,  Jinlong Zhang 1,  Ying Tang 3,  Changxing Qi 4,  Yonghui Zhang 5
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
  • 2 Laboratory of Clinical Research Center, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, PR China.
  • 3 Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, PR China. Electronic address: 10280921@qq.com.
  • 4 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; School of Pharmaceutical Sciences & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, PR China. Electronic address: qichangxing@hust.edu.cn.
  • 5 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: zhangyh@mails.tjmu.edu.cn.
PMID: 41512353 DOI: 10.1016/j.bioorg.2026.109473
Abstract

Under the guidance of the HSQC-based DeepSAT method, nine undescribed citrinin derivatives, including six citrinin monomers, citriniorls A - F (1-6), and three dimers, decitrinols A - C (7-9), along with three known analogues, were quickly isolated from the endophytic fungus Penicillium citrinum TJ507 collected from Hypericum wilsonii N. Robson. Their structures and absolute configurations were confirmed by comprehensive spectroscopic analyses, X-ray single-crystal diffraction, CASE algorithms and ECD calculation. Notably, compound 9 represents the first example of 8,9-seco-citrinin dimers. Biologically, citriniorl A (1) showed moderate activation activity towards SIRT1, with EC50 value of 5.8 μM and the molecular docking experiment further identify the binding modes of compound 1 and SIRT1, which provided a potential natural product to cure metabolic disorders.

Keywords

Citrinin derivatives; DeepSAT; Penicillium citrinum; SIRT1 activator.

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