SIRT2 inhibitors(University of Freiburg)

In our study, we aimed to investigate the effect of SIRT2 inhibition on function, fibrosis and inflammation in liver fibrosis induced by D‐Galactose (D‐Gal) administration. A total of 32 3‐month‐old Sprague Dawley rats were used in the study. Rats were divided into 4 groups as Control, d‐Gal, Solvent+d‐Gal, d‐Gal+AGK2+Solvent. d‐Gal (150 mg/kg/day), AGK‐2 (10 µM/bw) as a specific SIRT2 inhibitor, 4%DMSO + PBS as a solvent was applied to the experimental groups and physiological saline was applied to the control group for 10 weeks. All applications were performed subcutaneously. Histological fibrotic changes were studied in the liver tissues by Masson's trichrome staining, hematoxylin and eosin staining and immunohistochemistry and the levels of selected factors were determined by quantitative reverse transcription‐polymerase chain reaction, western blot analysis, and immunohistochemical analysis. Biochemical parameters and Paraoxonase levels were determined in the plasma. d‐Galactose administration increased AST, AST‐ALT Ratio, APRI, SIRT2 protein expression, IL1β, TGF β, β‐catenin, Type I collagen, Type III collagen and α‐SMA, collagen fiber density and histopathological score. ALT and lipid panels were not changed and paraxonase plasma level was shown to decrease. These effects were largely blocked by the SIRT2 inhibitor AGK2. These findings suggest that SIRT2 inhibition attenuates d‐Gal‐induced liver injury and that this protection may be due to its antifibrotic and anti‐inflammatory activities.

We aimed to conduct in silico screening of the potential phytoconstituent from a natural product database to find SIRT2 inhibitors.

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by behavioral and mental symptoms as well as a progressive loss of cognitive ability. Since SIRT2 may be detrimental to neurological illnesses, it is a prime target for research into SIRT2 inhibitors.

To identify the SIRT2 inhibitors and their role in AD.

We have utilized NPAtlas database and screened using pharmacophore-based virtual screening, molecular docking, and simulation. The Natural Products Atlas provides unrestricted access to various natural products derived from bacteria and fungi, allowing researchers to investigate and visualize the extensive chemical diversity in the natural world.

From in silico screening data, we have found phytoconstituents that could function as SIRT2 inhibitors. Six phytoconstituents were identified using pharmacophore-based virtual screening. According to molecular docking, Kurasoin B outperformed the reference molecule regarding binding energy. Kurasoin B exhibited a binding affinity of -12.543 kcal/mol, whereas the binding affinity of the reference molecule was -12.089 kcal/mol. The Kurasoin B complex with SIRT2 was determined to be stable throughout the simulation by performing MD simulation, with an RMSD of 2.88 (Å), whereas the reference and free protein displayed RMSDs of 3.74 and 4.70 (Å), respectively.

In silico studies and data analysis, suggest that Kurasoin B may be able to suppress the SIRT2 protein for managing AD.