Molecular interactions of some natural ligands to explore their mechanism of actions as PDE-4B and 4D inhibitors in psoriasis: A molecular docking study

Abstract

Psoriasis is an autoimmune and inflammatory disease, that significantly affects human well-being. The chances of relapses of psoriasis are high even after steroidal therapy and other medicines. The proper treatment is unavailable due to a lack of understanding of the pathophysiology of this disease. Phosphodiesterase enzyme subtypes (PDE-4B and PDE-4D) have been implicated in the pathophysiology of psoriasis because this enzyme inhibitor elevates the level of C-Amp and hence reduces the features of inflammation. Recent researches also demonstrated the role of the Phosphodiesterase enzyme in psoriasis. Therefore, in this study, molecular docking analysis was carried out on twelve natural ligands that have been proven to be anti-psoriatic candidates via preclinical studies via different animal models but their mechanism of action was not explored yet. The chemical structures of the natural ligands were prepared using ChemSketch 2015 (Free version). The AutoDock Tool 1.5.6 was employed for the molecular docking studies. The results indicated that all ligands interacted with the targets in the active sites and Capsaicin and Hypericin inhibited PDE-4B and Gossypol inhibited PDE-4D enzymes, respectively, via interacting with responsible amino acids of the targets and demonstrating significant binding energies.