In Silico Screening of Potential Phytochemical Inhibitors against Human Hematopoietic Prostaglandin D2 Synthase (hH-PGDS) for Anti-Allergic and Anti-Inflammatory Drug Development

Abstract

Human hematopoietic prostaglandin D2 synthase (hH-PGDS) is a key enzyme responsible for the biosynthesis of prostaglandin D2 (PGD2), an important lipid mediator involved in allergic responses, inflammation, asthma, and immune regulation. Inhibition of hH-PGDS represents a promising therapeutic strategy for developing novel anti-allergic and anti-inflammatory agents. The present study aimed to identify potential phytochemical inhibitors targeting hH-PGDS using structure-based virtual screening and molecular docking approaches.
A total of 890 phytochemical compounds were retrieved from the PubChem database and screened against the active site of hH-PGDS (UNIPROT ID: O60760; PDB ID: 5AIV) using LibDock protocol implemented in BIOVIA Discovery Studio 2019. The experimentally reported indole inhibitor of hH-PGDS was selected as the reference compound, exhibiting a LibDock score of 123.347 and CDOCKER interaction energy of 30.0771. Based on LibDock ranking, 39 phytochemicals were selected for further evaluation. The top five candidates were subsequently analyzed using the CDOCKER docking algorithm to evaluate binding affinity, interaction pattern, and molecular stability within the enzyme active site.
The potential identified 2 phytochemicals (Salvianolic acid A Compound CID: 5281793 & Calceolarioside B Compound CID: 5273567) demonstrated favorable binding interactions with important catalytic and active-site residues of hH-PGDS, suggesting their potential inhibitory activity. The screened compounds may serve as promising lead molecules for further experimental validation and development of novel anti-inflammatory and anti-allergic therapeutics.