Structural modification of a specific antimicrobial lead against Helicobacter pylori discovered from traditional Chinese medicine and a structure-activity relationship study.
Psoralen (1a) was found to be a specific and potent antimicrobial lead against Helicobacter pylori (H. pylori) from a traditional Chinese medicine (TCM) in the bioassay directed isolation. A series of structurally diverse analogues of 1a were thus designed and synthesized to improve the antimicrobial potency, some of which showed more potent activities than the lead compound (1a) against H. pylori. Among them, compound 25a is 16-fold stronger (MIC = 0.39 μg/mL) than 1a (MIC = 6.25 μg/mL), and is even potent than the positive control metronidazole (MIC = 0.50 μg/mL). The in vitro antimicrobial activities against H. pylori of these structurally diverse analogues based on the scaffold of 1a have also led to an outline of structure-activity relationship.
Zhang
Bang-Le
BL
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
Fan
Cheng-Qi
CQ
Dong
Lei
L
Wang
Fang-Dao
FD
Yue
Jian-Min
JM
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008516:Medicine, Chinese Traditional; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents