In Silico Analysis and Comparative Molecular Docking Study of FDA Approved Drugs with Transforming Growth Factor Beta Receptors in Oral Submucous Fibrosis.

Abstract

Oral sub-mucous fibrosis (OSMF) is a severe crippling malignant disorder which affects the oral mucosa. The transforming growth factor beta (TGF-β) is one of the cytokines involved with the cell proliferation, cell growth and apoptosis. Several traditional and synthetic medications have been tried in OSMF. This study attempts to identify the FDA approved drugs (including both synthetic and herbal medications) with least side effects, highest efficacy and robust dynamic mechanism for the treatment of OSMF. A ligand library comprising of FDA approved drug compounds was prepared using ChEMBL database. Molecular docking was carried out using GOLD suite 5.2.2. The docked complexes which had the highest binding affinities and lowest energy were deployed to a molecular dynamic simulation using MDweb server. Further, SwissADME was used to study ADME, physicochemistry, drug-likeness, pharmacokinetics and medicinal chemistry friendliness properties. Our docking results suggest that ligands-Curcumin, Curcumin Pyrazole and Demethoxycurcumin, which are all herbal in nature, have a better binding affinity and the best docking scores for both TGF-β type Iand TGF-β type II receptors. The molecular dynamics study discerns that the structures have become more stable with less energy. The pharmacokinetics and pharmacodynamics analysis, physicochemical properties and toxicity prediction suggest that Curcumin is the optimal lead compound and holds the potential to be used as an effective drug for the treatment of OSMF. Curcumin, a FDA approved herbal compound, can be used as an effective drug for the treatment of OSMF.