Hansen Martin, Krogh Kristine A, Brandt Asbjørn, Christensen Jan H, Halling-Sørensen Bent
Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Environ Pollut. 2009 Feb;157(2):474-80. doi: 10.1016/j.envpol.2008.09.022. Epub 2008 Oct 30.
The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC(50)-values between 2.4 and 19.6 microM were obtained; however, one compound, nicarbazin exhibited an EC(50)-value above the maximum tested concentration (21 microM, 9.1 mg L(-1)). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC(50)-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT(50) of 4.1 days) and was unstable at low pH (DT(50) of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns.
采用土壤细菌生物测定法(倾注平板法)对8种抗球虫药的抗菌效力进行了测试,得到的半数效应浓度(EC(50))值在2.4至19.6微摩尔之间;然而,一种化合物尼卡巴嗪的EC(50)值高于最大测试浓度(21微摩尔,9.1毫克/升)。两种化合物那拉菌素和尼卡巴嗪的混合物效力具有协同性(大于相加作用),混合物的抗菌效力比根据其各自的EC(50)值所能解释的要强10倍。研究了pH、温度、氧气浓度和光照对罗苯哒唑和盐霉素转化的影响。罗苯哒唑通过光解作用发生转化(半衰期(DT(50))为4.1天),在低pH条件下不稳定(DT(50)约为4天);盐霉素仅在低pH条件下发生转化,后者转化为数量不明的产物。罗苯哒唑光解后及在低pH条件下的转化产物混合物的抗菌效力与母体化合物相当。最后,通过精确质量测量、i-FIT值(同位素模式拟合)和串联质谱裂解模式对罗苯哒唑的5种光转化产物进行了结构解析。