RECEPTOR-BASED VIRTUAL SCREENING TO FIND NOVEL INHIBITOR AGAINST TRYPTOPHAN HYDROXYLASE I BY BIOOXIDATION USING TRADITIONAL CHINESE MEDICINE DATABASE

摘要

Serotonin (5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPHl and TPH2 are the rate-limiting enzyme in the 5-HT biosynthesis process and play very important roles in many bio-oxidation functions. TPHl expression is mainly limited in the enterochromaffin cells and distributed in periphery such as skin, gut, pineal gland and TPH2 is exclusively expressed in neuronal cell types and is the predominant isoform in the central nervous system (CNS). Therefore, the novel TPH inhibitor, which is specifically inhibiting THPl for decreasing the negative effects in CNS, is very imperative. In this work, we performed receptor-based virtual screening against the TCMP database. Using a docking algorithm, AutoDock Vina combined with subsequent post-docking analyse, mol002291 was screened as a drug-like compound from TCMP database for the inhibitor of TPH. mol002291 could be developed as a novel prodrug for offering therapeutic avenues for a multitude of diseases linked to the bio-oxidation of peripheral serotonergic pathways, including gastrointestinal diseases such as irritable bowel syndrome and inflammatory bowel disease.