Activity and structure relationship of acridine derivatives against African trypanosomes.
Activity and structure relationship of acridine derivatives against African trypanosomes.
复制标题
吖啶衍生物抗非洲锥虫的活性和结构关系。
DOI：
--
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
R. Brun
中科院分区：
文献类型：
--
作者：
W. Obexer;C. Schmid;J. Barbe,;J. Galy;R. Brun
筛选了 48 个新合成的不同类别的吖啶衍生物的抗锥虫活性。他们通过基于荧光的体外测定中酯酶活性的抑制来测量对罗得西亚锥虫和布氏锥虫血流形式的剂量依赖性影响。对所研究的吖啶的 IC50 和 MIC 值进行分析后，很明显没有新化合物达到正在使用的杀锥虫药物的水平 (50 ng/ml)。大多数衍生物的 IC50 值在 1 至 10 微克/毫升范围内。来自不同类别吖啶的 9 种衍生物的体外活性低于 1 微克/毫升。通过比较这些化合物的IC50和MIC值，阐明了结构和对锥虫效应之间的相关性，在此过程中，没有注意到布氏锥虫和罗得西亚锥虫之间的药物敏感性存在显着差异。 9-硫代吖啶类中的二烷基氨基烷基衍生物比单烷基化的衍生物稍强。 1,2,3,4-四氢-9-硫代吖啶以与9-硫代吖啶相同的方式表现出较高取代侧链对杀锥虫活性的影响。 9-硫代吖啶的相应酮证实了由于二烷基氨基烷基侧链的衍生化而导致毒性增加的趋势。在 9-氨基吖啶系列中，侧链的延长并没有显着改变活性，但 IC50 值通常较低，在 0.13 至 1.2 微克/毫升之间。（摘要截断为 250 字）
48 newly synthesized acridine derivatives of different classes were screened for antitrypanosomal activity. They showed a dose dependent effect on Trypanosoma rhodesiense and T. brucei bloodstream forms measured by the inhibition of esterase activity in a fluorescence based in vitro assay. After analysis of the IC50 and MIC values of the investigated acridines it was obvious that no new compound reached the level of the trypanocidal drugs in use (50 ng/ml). Most of the derivatives had IC50 values in the range of 1 to 10 micrograms/ml. 9 derivatives from different classes of acridines were in vitro active below 1 microgram/ml. Correlations between structure and effect on trypanosomes have been elucidated by comparing the IC50 and MIC values of these compounds, in the course of which no significant differences in the drug susceptibility between T. brucei und T. rhodesiense was noticed. The dialkylaminoalkyl derivatives among the group of the 9-thioacridines were slightly more potent than the mono-alkylated ones. 1,2,3,4-tetrahydro-9-thioacridines showed the influence of higher substituted side chains on the trypanocidal activity in the same way as 9-thioacridines. The corresponding ketones of 9-thioacridines confirmed the tendency of increasing toxicity due to the derivatisation of the dialkylaminoalkyl side chain. Within the series of the 9-aminoacridines the elongation of the side chain did not markedly change the activity, however the IC50 values are generally low between 0.13 and 1.2 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)