Studies On Synthesis And Anti-inflammatory Activities Of Imidazolidine-2, 4-dione And Its Derivatives

Objective:PPAR-α/-δ/-γ, MMPs, PDE4 and LOX play significant roles in anti-inflammatory progress, such as the production and migration of inflammatory mediators as well as the inflammatory injuries induced by these mediators. Based on the 3D structures of these protein molecules, novel anti-inflammatory compounds were anticipated to be development in this research by molecular modification and virtual screening of imidazolidine-2,4-dione and its derivatives.Methods:Sequence alignments of primary structures,3D structure fitting and phylogenetic relationship analysis of these enzymes have been performed to choose the representative structure; eight enzymes were chose for docking. According to the results of molecule docking of imidazolidine-2,4-dione and its derivatives, target compounds were selected and designed to be acquired by organic synthesis. Aniline and its derivatives were the main raw materials of synthesis. Anti-inflammatory and analgesic activities were evaluated respectively by mice ear swelling model induced by croton oil and mice writhing test induced by acetic acid.Results:Representative receptor molecules that suit for virtual screening were found. Target molecules were selected from imidazolidine-2,4-dione and its derivatives through molecular modification and virtual screening. Ten chemicals were acquired by organic synthesis. Activity evaluation demonstrates that three of these target compounds could inhibit mice ear swelling induced by croton oil effectively. Conclusions:The virtual screening model of anti-inflammatory activity has been built. Target chemicals were acquired through molecular modification and virtual screening based on docking method. Three of the synthesized target compounds have anti-inflammatory effect. The results of this research show that it is a practical way to design novel drugs on the basis of the structure of essent enzymes.