2-Substituted-5-Nitroheterocycles: In Vitro Anti-Helicobacter pylori Activity and Structure-Activity Relationship Study

Helicobacter pylori infection is the main cause of gastritis and gastroduodenal ulcer disease, and is associated with gastric cancer. In order to develop new potential anti-Helicobacter pylori candidates, we have investigated the antimicrobial activity of some 2-substituted-5-nitroheterocycles against H. pylori. The anti-Helicobacter pylori activity of selected compounds along with commercially available antibacterial metronidazole was evaluated by comparing the inhibition zone diameters determined using the paper disc diffusion bioassay. The compounds that exhibited strong anti-H. pylori activity at concentration of 8-32 μg/disc (average of inhibition zone >20 mm) were further tested against 20 clinical isolates of H. pylori at lower concentrations. In general, we have identified a series of 5-nitroheterocyles including nitrofurans, nitrothiophenes and nitroimidazoles bearing a carboxaldehyde thiosemicarbazone or 2-substituted-1,3,4- thiadiazole residues in the 2-position of the 5-nitroheteroaryl ring as potent anti- Helicobacter pylori agents. It was found that chloro-/ amino-/ mercapto-substituted 1,3,4-thiadiazole moiety attached to 5-nitroheteroaryl ring served as promising C-2 substituents for 2-substituted-5-nitroheterocycles. The Structure-activity relationship of this series indicates that both the structure of the nitroaryl scaffold and the C-2 attached residue have dramatic impact on anti-Helicobacter pylori activity.