PJB-2025-361
Pharmacoinformatics and In Vitro Evaluation of Plant-Origin Amorinin and Ferruginin A as Novel Helicobacter pylori Urease Inhibitors: Insights from Molecular Docking, ADMET Prediction, and Cytotoxicity Studies
Muhammad Taj Akbar
Abstract
Helicobacter pylori is a main cause of gastrointestinal disorders. Its virulence and ability to survive in the gastrointestinal tract is due to urease. It is imperative to develop new inhibitors of urease as a result of increasing antibiotic resistance. In this study, the approach of pharmacoinformatics analysis integrated with in vitro experimentation is used to find and study possible inhibitors of H. pylori urease. A library of 2,213 compounds was prepared and docking studies were performed using the Molecular Operating Environment (MOE) to select the most promising possible inhibitors. The compounds were subject to prediction of the ADMET profiling using SwissADME and ProTox in order to determine drug-likeness and to determine toxicity. The most promising inhibitors as determined by study of bioinformatics includes amorinin (PubChem ID 10253728) and ferruginin A (PubChem ID 5281773), which were then further studied in vitro. Cytotoxicity studies were conducted on HeLa cells and inhibition studies on H. pylori urease. From the bioinformatics study, amorinin and ferruginin A appeared as the two leading hits with -14.5667 and -14.3955 for the docking score respectively and with binding energy for key residues of the H. pylori urease enzyme. Both compounds passed ADMET results and were determined to be suitable as drug-like compounds with minimal toxicity. In vitro both amorinin and ferruginin A showed competitive inhibition of urease since IC Go value was found to be 4.5 µM and 6.2 µM respectively. Cytotoxicity studies indicated that the IC Go obtained for amorinin was 15.3 µM and that for ferruginin A was 18.7 µM which indicates they are cytotoxic in a dose-related manner. The in-silico screening of possible inhibitors combined with experimental validation has shown promising results in the identification of amorinin and ferruginin A as possible drug leads for the treatment of H. pylori infection. These compounds have potent urease inhibition and suitable pharmacokinetics. Further in vivo studies are needed to study their clinical efficacy in the treatment of gastrointestinal disorders associated with H. pylori.
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