STRUCTURE-ACTIVITY-RELATIONSHIPS OF ANTIFILARIAL ANTIMYCIN ANALOGS - A MULTIVARIATE PATTERN-RECOGNITION STUDY
STRUCTURE-ACTIVITY-RELATIONSHIPS OF ANTIFILARIAL ANTIMYCIN ANALOGS - A MULTIVARIATE PATTERN-RECOGNITION STUDY
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DOI：
10.1021/jm00163a023
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发表时间：
1990-01-01
影响因子：
7.3
通讯作者：
STABLES, JN
中科院分区：
文献类型：
--
作者：
SELWOOD, DL;LIVINGSTONE, DJ;STABLES, JN
用计算化学和多元统计技术研究了一系列新型抗丝虫抗菌素A1类似物的构效关系。以这种方式计算的物理化学描述符包含了根据化合物的体外抗丝虫病活性对其进行分类的有用信息。该方法生成了53个参数描述符集，并使用多变量模式识别程序Arthur进行了简化。回归分析得到几个有统计学意义的回归方程：-LOG体外活性=0.017 MP+0.65log P-0.81ESDL10-7.33(R=0.9)。有了这个方程式，就有可能对更多未经检验的类似物进行预测。分析表明，膜或脂类的溶解性是生物活性的一个重要决定因素，这与化合物作为角质层葡萄糖摄取干扰物的主要作用模式相一致。
The structure-activity relationships for a series of novel antifilarial antimycin A1 analogues have been investigated by using computational chemistry and multivariate statistical techniques. The physiochemical descriptors calculated in this way contained information which was useful in the classification of compounds according to their in vitro antifilarial activity. This approach generated a 53 parameter descriptor set, which was reduced with a multivariate pattern recognition package, ARTHUR. Regression analysis of the reduced set yield several statistically significant regression equations; e.g.-log in vitro activity = 0.017 mp + 0.65 log P - 0.81ESDL10 - 7.33 (R = 0.9). With use of this equation, it was possible to make predictions for further untested analogues. The analysis indicated that membrane or lipid solubility is an important deteminant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake.