Pharmacophore Modeling of Furanosyl Borate Diester: An Attempt to Combat Antibiotic Resistance Induced Helicobacter pylori Quorum Sensing Mediated Peptic and Duodenal Ulcer

Mohit Kumar, Aaliya Naaz, A

Abstract

Helicobacter pylori is a gram-negative, microaerophilic bacterium found usually in the stomach of a person with chronic gastritis and gastric ulcers. More than 50% of the world’s population harbor H. pylori in their upper gastrointestinal tract. About 85% of people infected with H. pylori never experience symptoms or complications. Individuals with chronic gastritis and infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers, MALT lymphoma, the pathogenesis of gastric cancer and several extra-gastric diseases. No vaccines are developed yet and the bacterial antibiotic resistance has been a growing concern. Helicobacter pylori produce virulence and antibiotic resistance through quorum sensing mechanisms by generating AI-2. Inhibition of quorum sensing would be a novel approach for the effective treatment of antibiotic-resistant strains of H. pylori. Chemical nature of AI-2 is furanosyl borate diester which is generated from 4,5-dihydroxy 2,3-pentanedione (DPD). But there are no synthetic congeners of AI-2 and DPD compounds tested against H. pylori till date. Therefore, it is the aim of the present study to design some potent AI-2 and DPD compounds under the framework of pharmacophore modeling.

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