Effects of acridines on bacterial plasmid replication and endotoxin.
Different amino- and imino-acridines were systematically synthesized. The antibacterial, antiplasmid, antimotility and endotoxin complexing effect of acridines were studied, when antibacterial effect of the compounds was compared on E. coli. Aminoderivatives were more active than imino-acridines. The N-heptyl-9-imino-acridine was able to select lon minus mutants in the E. coli culture, however, the other acridines tested were ineffective in this respect. The iminoacridines inhibited the motility of Proteus vulgaris more effectively than aminoderivatives. The antimotility action of the acridines was also dependent on the ionic content of the media. The antiplasmid effect was measured on an F-prime plasmid of E. coli LE140 strain. Iminoacridines had a more powerful antiplasmid effect than the amino-substituted derivatives. The majority of the compounds inhibited the intercellular plasmid transfer from E. coli. Kmr donor to a Na-azide resistant recipient. In this test the aminosubstituted derivatives were shown to be more effective inhibitors of conjugation than the imino-substituted compounds. Endotoxin formed complexes with N-butylamino. N-propy-lamino and imidoderivatives. However, complex formation of N-ethyl-, N-heptyl-, N-diethylaminoethyl- and N-diethylamino-propyl-acridines were different. Correlations between molecular orbitals and the antibacterial effects are also discussed.
Barbe
J
J
GERCTOP-URA CNRS 1411, Faculte de Pharmacie, Marseille, France.
Mándi
Y
Y
Hevér
A
A
Petri
I
I
Galy
J P
JP
Molnár
J
J
D000166:Acridines / Q000378:metabolism / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects*; D015394:Molecular Structure; D010957:Plasmids / Q000378:metabolism*; D011514:Proteus vulgaris / Q000187:drug effects*; D059004:Topoisomerase I Inhibitors
D000166:Acridines; D004731:Endotoxins; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I