Indolo[3,2-<i>b</i>]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by <i>Aeromonas sobria</i> and Alpha-Hemolysin Produced by <i>Staphylococcus aureus</i>

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 alphahemolysin 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.

Morin Protects Channel Catfish From Aeromonas hydrophila Infection by Blocking Aerolysin Activity

“…However, the effect of morin on A. hydrophila is not investigated. Compared with four kinds of indolo[3,2- b ] quinoline, compounds against the activity of aerolysin-like hemolysin (ALH) produced by A. sobria , the mechanism and binding site of morin inhibiting AerA were determined using molecular dynamics and fluorescence quenching methods ( Takahashi et al, 2016 ). Moreover, the in vivo effect against A. hydrophila infection has been evaluated by a channel catfish model.…”

Palmatine Inhibits the Pathogenicity of Aeromonas hydrophila by Reducing Aerolysin Expression

“…Eizo Takahashi et al synthesized Indolo[3,2-b] quinolone derivatives and investigated the inhibitory effect against aerolysin activity in the supernatants of A. hydrophila and Aeromonas sobria strains. The results showed that the derivatives could directly neutralize the activity of aerolysin by hemolysis assay and were hopeful candidates in discovery of drugs by decreasing bacterial virulence [ 46 ]. However, some of the derivatives showed both anti-bacterial and anti-virulence bifunctional activities, indicating that the drug could provide selective pressure to bacteria and could result in resistance in the future.…”

Luteolin decreases the pathogenicity of Aeromonas hydrophila via inhibiting the activity of aerolysin

“…Moreover, indolo [3,2-b] quinolones have been identified as good candidates for anti-virulence drugs by inhibiting the activity of AerA like hemolysin of A. sobria. However, the mechanism and major binding sites were not determined by the authors [47]. Molecular dynamics (MD) simulations, a promising tool for drug identification, have been widely applied to determine the binding modes and binding energies of ligand-target interactions.…”