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 Original Research Article

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 (LD50) to human erythrocytes (97 ± 6 μM) and the NB1RGB cell line (111 ± 20 μM) and remarkable anti-bacterial activity (MIC) toward E. coli K12 W3110 (7.9 μM). 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.