鹿蹄素类化合物的抗菌定量构效关系研究

The Quantitative Structure-Activity Relationship of the Antibiotic Properties of Pyrolines

关键词:  鹿蹄素  抗菌活性  定量构效关系  Hansch法

Key words:  pyroline  antibiotic properties  quantitative structure-activity relationship(QSAR)  Hansch

摘要:

目的研究鹿蹄素类化合物的抗菌定量构效关系。方法以鹿蹄素为先导化合物，采用聚类分析法，合成了12个新氢醌化合物。选取金葡萄球菌84184为活性常数提取的致病菌。结果所得Hansch法定量构效关系方程为：lg1/MIC=0.035 0 π- 0.015 3 π2+0.178 4 σ+0.002 0 MR-1.621 3 I+4.441 5，n=13，r=0.808 9，F=2.65(α=0.05)。以未经回归统计分析的异丙基氢醌进行验证，发现该方程对化合物的活性预测有一定的参考意义。通过挑选作用显著的参数，发现指示变量I与抗菌活性的58%相关，从而提出：氢醌类化合物是通过氧化还原的反应而显示其抗菌活性的作用机理。结论本实验对进一步寻找更有效的鹿蹄素衍生物和阐明其作用机理，提供了一定的线索和依据。

Abstract:

OBJECTIVE To study the quantitative structure-activity relationship of the antibiotic properties of a series of pyrolines. METHODS Pyroline was acted as a lead compound and new twelve hydroquine compounds were synthesized. Combined with clinic practice, staphylococcus was selected as a pathogenic bacterium by which effective coefficients were measured. RESULTS It followed: Hansch QSAR equation was lg1/MIC=0.035 0π-0.015 3π2+0.178 4σ+0.002 0 MR-1.621 3 I+ 4.441 5, n=13, r=0.808 9, F=2.65(α=0.05). When iso-propylhydroquinone were used to prove the equation, there were some certain effective significance for its equation forecasting compounds' activity. Through selecting significant action parameters, it was followed that there was 58% correlation between indicator variance (I) and antibacterial activity. Therefore, antibacterial mechanism of hydroquinones was carried out by oxidization and reduction reaction. CONCLUSION The experiment provides some certain clue and basis for finding farther effective pyrolines and explaining its action mechanism.