Investigation of enzyme inhibition, serum protein protective effects, and molecular docking studies of mixed-ligand ruthenium(<sc>ii</sc>) polypyridyl complexes

Five new ruthenium(ii) complexes-[Ru(eta 2-N,S-mpy)(eta 1-S-mpy)(tptz)] (Ru1), [Ru(eta 2-N,S-mbtz)(eta 1-S-mbtz)(tptz)] (Ru2), [Ru(eta 2-N,S-mpt)(eta 1-S-mpt)(tpy)] (Ru3), [Ru(eta 2-N,S-mbtz)(eta 1-S-mbtz)(tpy)] (Ru4), and [Ru(eta 2-N,S-mpy)(eta 1-S-mpy) (tpy)] (Ru5)-were synthesized and characterized using elemental analyses, IR, 1H and 13C NMR, and electronic absorption spectroscopy. The molecular structure of the representative complex Ru1 was determined crystallographically. The coordination geometry in Ru1 was found to be distorted octahedral with tptz coordinated to the ruthenium centre in a kappa 3 mode and two 2-marcaptopyridine ligands coordinated in kappa 2 and kappa 1 modes. The synthesized complexes were evaluated for their inhibitory activity against intracellular enzymes, such as amylase, lipase, trypsin, and pepsin, as well as their serum protein protecting activity. Lipase, trypsin, and pepsin displayed inhibitory effects in the presence of the synthesized complexes and ligands, with observed IC50 values in the range of 10-6 M, whereas amylase activity was found to be enhanced. In line with other pharmacologically active Ru(ii) compounds, serum protein binding studies were performed using both the N,S ' and N,N ' donor ligands, as well as the ruthenium(ii) complexes Ru1-Ru5. These studies revealed that the binding efficiency of the complexes surpassed that of the corresponding ligands.