biostudies-literatureGuo XNational Natural Science Foundation of China (National Science Foundation of China)183https://www.ebi.ac.uk/biostudies/studies/S-EPMC11228022biostudies-literatureUnknown9(1)Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose.Signal transduction and targeted therapyA deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori.PMC11228022321410038200357561972384Jiang JZeng QXu MLu XGuo XSong DChen FWei WYou XZhao XFan TZhao LZhang ZZhang XPang JWang YFeng SfalseA deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori.Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose.2024-01-01T00:00:00Z2024 Jul2026-06-01T07:37:35.54Z2025-04-04T11:25:14.621ZS-EPMC112280223897290410.1038/s41392-024-01895-0