Bridge-linked bis-quaternary ammonium anti-microbial agents: relationship between cytotoxicity and anti-bacterial activity of 5,5'-[2,2'-(tetramethylenedicarbonyldioxy)-diethyl]bis(3-alkyl-4-methylthiazonium iodide)s.
We examined the correlation between the anti-bacterial activity against Escherichia coli and the cytotoxicity of five synthesized bridge types of bis-quaternary ammonium compounds (bis-QACs) as follows: thioether type, 4,4'-(p-xylydithio)bis(1-octylpyridinium iodide) (4DTBP-X,8); amide type, N,N'-tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) (4BCAP-4,12), N,N'-(phenylene)bis(1-octyl-4-carbamoylpyridinium iodide) (4BCAP-P,8); anti-amide type, 4,4'-(tetramethylenedicarbonyldiamino)bis(1-octylpyridinium iodide) (4DCABP-4,8), 4,4'-(phenylenedicarbonyldiamino)bis(1-octylpyridinium iodide) (4DCABP-P,8); ester type, 4,4'-(1,6-hexamethylenedioxydicarbonyl)bis(1-dodecylpyridinium iodide) (4DOCBP-6,12); and an anti-ester type, 5,5'-[2,2'-(tetramethylenedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium iodide) (5DEBT-4,n, The letter n indicates the carbon number of the alkyl group). 5DEBT-4,8 showed low cytotoxicity (LD(50)) to human erythrocytes (97+/-6microM) and the NB1RGB cell line (111+/-20microM) and remarkable anti-bacterial activity (MIC) toward E. coli K12 W3110 (7.9microM). Moreover, 5DEBT-4,8 indicated 1144 conformers by global minimum analysis and had two minimum dGW (solvation free energy) points as well as 4DTBP-6,8, which had been previously examined and concluded to be a significant useful anti-bacterial compound.
Ohkura
Kazuto
K
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, 2-1 Minamijosanjima-cho, Tokushima 770-8506, Japan.
Sukeno
Akiko
A
Nagamune
Hideaki
H
Kourai
Hiroki
H
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000644:Quaternary Ammonium Compounds