title: Indolo[3,2-b]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by Aeromonas sobria and Alpha-Hemolysin Produced by Staphylococcus aureus.
abstract: In an attempt to discover inhibitory compounds against pore-forming toxins, some of the major toxins produced by bacteria, we herein examined the effects of four kinds of indolo[3,2-b]quinoline derivatives on hemolysis induced by the aerolysin-like hemolysin (ALH) of Aeromonas sobria and also by the alpha-hemolysin of Staphylococcus aureus. The results showed that hemolysis induced by ALH was significantly reduced by every derivative, while that induced by alpha-hemolysis was significantly reduced by three out of the four derivatives. However, the degrees of reduction induced by these derivatives were not uniform. Each derivative exhibited its own activity to inhibit the respective hemolysin. Compounds 1 and 2, which possessed the amino group bonding the naphthalene moiety at the C-11 position of indolo[3,2-b]quinoline, had strong inhibitory effects on the activity of ALH. Compound 4 which consisted of benzofuran and quinoline had strong inhibitory effects on the activity of alpha-hemolysin. These results indicated that the amino group bonding the naphthalene moiety of compounds 1 and 2 assisted in their ability to inhibit ALH activity, while the oxygen atom at the 10 position of compound 4 strengthened its interaction with alpha-hemolysin. These compounds also suppressed the hemolytic activity of the supernatant of A. sobria or A. hydrophila, suggesting that these compounds were effective at the site of infection of these bacteria.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nihon Pharmaceutical University.
authors.forename: Eizo
authors.initials: E
authors.lastname: Takahashi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Fujinami
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyoshi
authors.forename: Sakae
authors.initials: S
authors.lastname: Arimoto
authors.forename: Tomoe
authors.initials: T
authors.lastname: Negishi
authors.forename: Keinosuke
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000333:Aeromonas / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects*; D006460:Hemolysin Proteins / Q000378:metabolism / Q000633:toxicity*; D006461:Hemolysis; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D012756:Sheep
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D011804:Quinolines; C021091:staphylococcal alpha-toxin