In Silico analysis of the effects of selected interleukin 1-beta inhibitors on ADAMTS5

Osteoarthritis (OA) is a degenerative joint damage involving the inflammatory process. Many small molecules are being used to reduce and stop the inflammatory response in the treatment of OA. In the presented study, it was aimed to perform in silico analyzes of the effects of selected IL-1β inhibitors on ADAMTS5. For this purpose, Apigenin, Butein, Curcumin, Gallic acid, Harpagocyte, Oleuropein, Hyperforin, Quercetin, Wogonin, EGCG and Resveratrol molecules, which may have IL-1β inhibitory properties, were compared with Aldumastat, an ADAMTS5 inhibitor, in terms of affinity and ADMET properties. Molecular docking analyzes and affinity values were calculated with the Autodock Vina program, and 3D complex structures of selected molecules were created with ADAMTS5. The ADAMTS5 binding sites and bond types of the molecules were comparatively examined with BIOVIA Discovery Studio software. After docking, ADAMTS5 protein-ligand total energy calculations were made with Swis-Pdb Viewer software. Absorption, Distribution, Metabolism, Excretion, Toxicological (ADMET) properties of selected molecules were evaluated with admetSAR software. The negative affinities of EGCG, Apigenin, Oleuropein and Wogonin to the active site of ADAMTS5 were calculated to be the highest, and among these molecules, Oleuropein and Wogonin were found to have the highest oral bioavailability and intestinal absorption in terms of ADMET properties, and the lowest hepatotoxic and nephrotoxic properties. We believe that the findings obtained are a guide for in vitro and in vivo studies, and as a result of in silico analysis, these molecules with ADAMTS5 inhibitor potential should be examined with more detailed molecular analyzes under in vitro and in vivo conditions. Keywords: Osteoarthritis, ADAMTS5, IL-1, In silico, Autodock