Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells.
Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
Chih-Shiang
CS
Chang
Ju-Fang
JF
Liu
Hwai-Jeng
HJ
Lin
Chia-Der
CD
Lin
Chih-Hsin
CH
Tang
Dah-Yuu
DY
Lu
Yu-Ting
YT
Sing
Li-Yu
LY
Chen
Min-Chuan
MC
Kao
Sheng-Chu
SC
Kuo
Chih-Ho
CH
Lai
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001562:Benzimidazoles; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori