抗日本血吸虫病活性物质——溴乙酸酯类定量构效关系的研究

STUDIES ON THE QUANTITATIVE STRUCTUREACTIVITY RELATIONSHIP OF THE SCHISTOSOMICIDAL SUBSTANCES——BROMOACETIC ESTERS

摘要: 本文用HMO法机算了26个有抗日本血吸虫病活性的溴乙酸酯类,求得它们的各项HMO指标。测定了BrCH₂CO₂—(?)—NHOCCH₃的lgP值,求得π_BrCH₂CO₂,从而推算出这些溴乙酸酯的lgP值。逐步回归分析证明,E_ICMO、lg²P和lgP值同生物活性相关,与文献关于卤代乙酸衍生物的生理作用机制的报道一致。算得的最适lgP值为1.09,也在文献报道的抗血吸虫病药物的lgP值范围内。用所得的Hansch方程预测,化合物BrCH₂CO₂—(?)—CH=N—(?)的生物活性较高,计算值与实测值基本相符。

Abstract: The quantum mechanical indices of 26 antischistosomal bromoacetic esters were computed by the HMO method. The lgP value of BrCH₂CO₂ NHCOCH₃ was determined, π_BrCH₂CO₂, was calculated, and the lgP values of these bromoacetic esters were thus obtained. Progressive regression analysis indicated that lg²P, lgP and E_LEMO were related to the biological activities, which were supported by the mechanism of physiological action of halogenoacetic acid derivatives reported in the literature. The optimum lgP value calculated (1.09) was within the range of lgP values of the schistosomicides in the literature. The Hansch equation obtained predicted that BrCH₂CO₂CH=N may have somewhat higher biological activity, and the value calculated was in fair accordance with the value determined.