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

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.