Metronidazole-flavonoid derivatives as anti-Helicobacter pylori agents with potent inhibitory activity against HPE-induced interleukin-8 production by AGS cells.
Three series of metronidazole-flavonoid derivatives were generated and evaluated for antimicrobial activity against H. pylori. Among these compounds, high anti-H. pylori activities were observed in isoflavones derivatives 4-7, 19, and 20 but exhibited no inhibitory activity against other sorts of bacteria and fungi, for example, Streptococcus pneumoniae, Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence, and Aspergillus niger. Genistein derivative 6 with the potent activity (MIC=0.39 microg mL(-1)) was >50-fold more than metronidazole, and comparable to the positive control amoxicillin. Additionally, compound 6 can significantly attenuate the increase in interleukin-8 (IL-8) levels in the AGS cells stimulated by H. pylori water extract (HPE) at concentrations of 15, 30, and 60 micromol L(-1), which did not show any effects on the cell viability.
Li
Huan-Qiu
HQ
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
Xu
Chen
C
Li
Hong-Sen
HS
Xiao
Zhu-Ping
ZP
Shi
Lei
L
Zhu
Hai-Liang
HL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009682:Magnetic Resonance Spectroscopy; D008795:Metronidazole / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization
D000900:Anti-Bacterial Agents; D005419:Flavonoids; D016209:Interleukin-8; D008795:Metronidazole