Durmaz R, Köroğlu M, Küçükbay H, Temel I, Ozer M K, Refiq M, Cetinkaya E, Cetinkaya B, Yoloğlu S
Department of Clinical Microbiology, Faculty of Medicine, Inönü University, Malatya, Turkey.
Arzneimittelforschung. 1998 Dec;48(12):1179-84.
In previous studies many benzimidazole, imidazole and benzothiazole derivatives had been synthesized and their antimicrobial activities were tested in vitro conditions. Four of these compounds showed minimal inhibitory concentrations (MIC) of 5-25 micrograms/ml against standard strains and clinical isolates. In order to determine whether these four compounds can be used for therapeutic purpose, their serum MIC values and side effects on hepatic and renal functions were determined. Different concentrations of the compounds were tested on Wistar rats. Compound 1 was administered orally, intramuscularly and intravenously; compounds 2, 3 and 4 were given orally and intramuscularly. Blood samples were taken 4 and 24 h after administration of the compounds. Serum MIC values were investigated by bioassay and serum levels of biochemical parameters by autoanalyzer. None of the tested compounds showed antimicrobial activity at their serum concentrations. Although creatinine activity was found at normal levels in all experiments, compounds 1 and 2 caused a significant increase in blood urea nitrogen (BUN) level. The values of aspartate aminotransferase and/or alanine aminotransferase and/or alkaline phosphatase which are characteristic for liver function were generally found at high levels. According to these results, it can be concluded that the tested compounds caused damage in liver and biliary tracts without antimicrobial activity by their serum concentrations.
在以往的研究中,已合成了许多苯并咪唑、咪唑和苯并噻唑衍生物,并在体外条件下测试了它们的抗菌活性。其中四种化合物对标准菌株和临床分离株的最低抑菌浓度(MIC)为5 - 25微克/毫升。为了确定这四种化合物是否可用于治疗目的,测定了它们的血清MIC值以及对肝肾功能的副作用。在Wistar大鼠上测试了不同浓度的化合物。化合物1通过口服、肌肉注射和静脉注射给药;化合物2、3和4通过口服和肌肉注射给药。在给药后4小时和24小时采集血样。通过生物测定法研究血清MIC值,通过自动分析仪测定生化参数的血清水平。在所测试的化合物的血清浓度下,没有一种显示出抗菌活性。尽管在所有实验中肌酐活性都处于正常水平,但化合物1和2导致血尿素氮(BUN)水平显著升高。通常发现肝功能特征性的天冬氨酸转氨酶和/或丙氨酸转氨酶和/或碱性磷酸酶的值处于高水平。根据这些结果,可以得出结论,所测试的化合物在其血清浓度下没有抗菌活性,但会对肝脏和胆道造成损害。