药物定量结构——活性的分子连接性研究——Ⅱ.柱晶白霉素类、林可霉素类和林大霉素类的定量构效关系(QSAR)

MOLECULAR CONNECTIVITY STUDIES ON QUANTITATIVE STRUCTURE-ACTIVITY OF DRUGS Ⅱ. Quantitative Structure-Activity Relationships for Leucomycins, Lincomycins and Clindamycins.

用分子连接性的方法建立了柱晶白霉素类、林可霉素类和林大霉素类的QSAR方程式。柱晶白霉素衍生物的体外抗菌活性随一阶价分子连接值的增加与大环内酯3-羟基酯基的除去而增加。在25个NCH_3和NC_2H_5林可霉素衍生物中,计算体外抗藤黄八迭球菌的最适一阶价分子连接值(~1X^(v^0))分别为11.7583与12.2394,林大霉素类最适~1(X^v^0)为11.3604。本文与Martin对该三类衍生物所建立的Hansch法进行了比较,两法结果几乎一致,而且基于计算的分子连接性法的统计学指标优于赖经验参数而得的Hansch法。

Equations of quantitative structure-activity relationships for Ieucomycins, lincomycins and clindamycins have been established by the method of molecular connectivity. The in vitro antibacterial activity of derivatives of the leucomycin complex increases with increasing the firstorder term of valence molecular connectivity (~1χ~v) and removal of esterification of the 3-hydroxy of the macrolide ring. In the series of NCH_3 and NC_2H_5 lincomycins, an optimum ~1χ^(v^0) of 11.7583 and of 12.2394 was calculated respectively for in vitro activity vs Sarcine lutea An optimum ~1χ^(v^0) of 11.3604 was calculated too. It was compared with Hansch method for these three series of derivatives set by Martin. Two methods give almost the same results. Molecular connectivity method based on calculation is found to have a more significant correlation in statistics than Hansch method which depends on empiric parameters.