Bactericidal effect of plaunotol, a cytoprotective antiulcer agent, against Helicobacter pylori.
In order to investigate the bactericidal effect of plaunotol, an oily antiulcer agent, against Helicobacter pylori, comparative studies were conducted using its derivatives, M-4, M-5, and M-6, whose hydrophobicity decreased in the order of plaunotol > M-6 > M-5 > M-4 by log P determination. Plaunotol rapidly reduced the viability of H. pylori in vitro, and cell death was associated with cell lysis. In addition, plaunotol showed eightfold stronger bactericidal activity against H. pylori than M-6 and M-5, while the compound with the lowest hydrophobicity, M-4, showed no bactericidal activity. The bactericidal activities of plaunotol and its derivatives were related to the hydrophobicity of these compounds. To investigate a possible interaction between these compounds and the cell membrane of H. pylori, their effects on liposomal membranes prepared from phosphatidylethanolamine and cardiolipin, which are known to be present in the membrane of H. pylori, were determined by detection of glucose release from the liposomes. Plaunotol showed eight-fold higher activity than M-6 and M-5, while M-4 showed no activity. The effects of plaunotol and its derivatives on liposomal membrane were therefore related to their bactericidal activities. In addition, it was confirmed that the bactericidal effect of plaunotol against H. pylori was neutralized by the liposomal membrane, and that plaunotol led to an increase in permeability of the membrane, as evidenced by measurement of the leakage of 260 nm absorbing-material from H. pylori. These results suggest that the bactericidal effect of plaunotol against H. pylori is due to the interaction between this compound and the bacterial cell membrane.
Koga
T
T
Biological Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Kawada
H
H
Utsui
Y
Y
Domon
H
H
Ishii
C
C
Yasuda
H
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects* / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D003998:Dicarboxylic Acids; D004224:Diterpenes; D005231:Fatty Acids, Unsaturated; D005233:Fatty Alcohols; D008081:Liposomes; C103995:plaunotol M-6; C103993:plaunotol M-4; C103994:plaunotol M-5; D005947:Glucose; C047686:plaunotol