In-Silico study to identify novel potassium competitive acid blockers for treating of peptic ulcer disease

Abstract

Peptic ulcer disease has the highest prevalence among gastrointestinal diseases. Among the medicines used in its treatment, Potassium Competitive Acid Blockers (P-CABs) represent a new class of drugs with several advantages over older classes. This research aims to identify compounds with high efficacy as potassium-competitive acid inhibitors for the treatment of peptic ulcer disease. An in-silico screening process was conducted using data from the Traditional Chinese Medicine Database. Subsequently, 3D-Pharmacophore models and molecular docking models were constructed. A screening of 57,288 compounds from the Traditional Chinese Medicine Database was performed using the in-silico model. Of these, 1,657 compounds matched the 3D-Pharmacophore model and successfully docked, with 28 compounds exhibiting better docking scores than the reference drug. The four most promising compounds selected were TCM1653, (-)-N-Demethylcrychine, Buphanidrine, and D-(1S,9R)-Hydrastine, all of which had lower docking scores than the reference drug and interacted with crucial amino acids. All four compounds meet Lipinski's Rule of Five criteria and exhibit favorable pharmacokinetic properties, rendering them promising candidates for the treatment of peptic ulcer disease.