Design, synthesis, and biological evaluation of new compounds effective against Helicobacter pylori

Aim: This study aimed to design, synthesize, and evaluate the activities of novel quinoline-sulfonate derivatives targeting critical biological targets of H. pylori using an artificial intelligence-assisted approach. Material and Method: Six quinoline-sulfonate derivatives designed using REINVENT 4 from literature-reported anti-H. pylori compounds were synthesized via O-sulfonylation and characterized by spectroscopic methods. Their urease inhibitory activities were determined using the Berthelot method against Jack bean urease. Results: Among the six synthesized compounds, only derivatives V and VI exhibited significant urease inhibitory activity. Compound V showed the highest activity with an IC₅₀ value of 6.49 mM, while compound VI displayed an IC₅₀ value of 16.88 mM. The IC₅₀ value of the positive control, thiourea, was determined to be 1.99 mM. Conclusion: The results demonstrated that trifluoromethyl-containing quinoline-sulfonate derivatives possess promising antiurease activity and that artificial intelligence-assisted design approaches may be utilized in the development of novel anti-H. pylori candidates.