Evaluation of the cytotoxic effects of bis-quaternary ammonium antimicrobial reagents on human cells

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• 作者：Nagamune ; H. ; Maeda ; T. ; Ohkura ; K. ; Yamamoto ; K. ; Nakajima ; M. ; Kourai ; H.
• 关键词：quaternary ammonium ; antimicrobial ; cytotoxicity ; 4BCAP-4 ; 12=N ; N&prime ; -tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) ; 4BCAP-6 ; 10=N ; N&prime ; -hexamethylenebis(1-decyl-4-carbamoylpyridinium iodide) ; 4DCABP-4 ; 10=4 ; 4&prime ; -(1 ; 4-tetramethylenedica
• 刊名：Toxicology in Vitro
• 出版年：2000
• 出版时间：April, 2000
• 年：2000
• 卷：14
• 期：2
• 页码：139-147
• 全文大小：295 K

文摘

The cytotoxic effects of newly synthesized bis-quaternary ammonium compounds (bis-QACs) and benzalkonium chloride were investigated on skin and blood cells, namely normal human epidermal keratinocytes of neonatal foreskin, a normal human skin fibroblast cell line NB1RGB, erythrocytes and a lymphoma cell line JM. The bis-QACs tested were 4,4′-(1,6-hexamethylenedithio)bis(1-octylpyridinium iodide) (4DTBP-6,8), N,N′-tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) (4BCAP-4,12), N,N′-hexamethylenebis(1-decyl-4-carbamoylpyridinium iodide) (4BCAP-6,10), 4,4′-(1,4-tetramethylenedicarbonyldiamine) bis (1-decylpyridinium iodide) (4DCABP-4,10), 4,4′-(1,4-tetramethylenedicarbonyldiamine) bis (1-dodecylpyridinium iodide) (4DCABP-4,12), 4,4′-(1,4-phenyldicarbonyldiamine)bis(1-dodecylpyridinium iodide) (4DCABP-P,12), and 4,4′-(1,6-hexamethylenedioxydicarbonyl)bis(1-dodecylpyridinium iodide) (4DOCBP-6,12). All bis-QACs consisted of two identical alkylpyridinium rings and bridge structure linking rings to each other have a methylene bridge but only 4DCABP-P,12 has a phenyl ring as a bridge. Most of the LD₅₀ values in acute cytotoxic assays of these bis-QACs tended to be lower than those of benzalkonium chloride. However, the comparison of the antibacterial activity against cytotoxic effects on several human cells revealed that bis-QACs, especially 4DTBP-6,8, have wide concentration ranges showing sufficient antibacterial activity and lower cytotoxic effect on human cells (except for 4DOCBP-6,12), although benzalkonium chloride caused significant human cell damage at the concentrations necessary for antibacterial activity. Moreover, judging from the LD₅₀ value of 4DTBP-6,8 [67 μ, a 6.7-fold higher concentration than the upper value of MIC] obtained in an artificial human skin model TESTSKIN, 4DTBP-6,8 is thought to be a more effective and safer antiseptic reagent for application to the skin surface than benzalkonium chloride. Taken together, bis-QACs are expected to be a promising new generation of antimicrobial QACs.