Anti-Inflammatory and Antioxidant Pyrrolo[3,4-d]pyridazinone Derivatives Interact with DNA and Bind to Plasma Proteins-Spectroscopic and In Silico Studies.

Abstract

From the point of view of the search for new pharmaceuticals, pyridazinone derivatives are a very promising group of compounds. In our previous works, we have proved that newly synthesized ligands from this group have desirable biological and pharmacokinetic properties. Therefore, we decided to continue the research evaluating the activity of pyrrolo[3,4-dpyridazinone derivatives. In this work, we focused on the interactions of five pyridazinone derivatives with the following biomolecules: DNA and two plasma proteins: orosomucoid and gamma globulin. Using several of spectroscopic methods, such as UV-Vis, CD, and fluorescence spectroscopy, we proved that the tested compounds form stable complexes with all biomacromolecules selected for analysis. These findings were also confirmed by the results obtained by molecular modeling. All tested pyridazinone derivatives bind to the ctDNA molecule via groove binding mechanisms. All these molecules can also be bound and transported by the tested plasma proteins; however, the stability of the complexes formed is lower than those formed with serum albumin.