Mannich碱类苯并异噻唑啉酮化合物抑菌活性及构效关系研究

摘要

Eleven mannich base derivatives of 1,2-benzisothiazolin-3-one were synthesized by the reaction of 1,2-benzisothiazol-3 (2H)-one(BIT),polyoxymethylene and substituted anilines through one-step method.The organisms used in the biological activity assay included Staphylococcus aureus,Staphylococcus albus,Escherichia coli,Bacillus subtilis,Klebsiella pneumoniae,Pseudo-monas aeruginosa.The results showed that most of the compounds exhibit excellent inhibition to the tested organisms except for Pseudomonas aeruginosa,with MIC50value from 4 mg·L-1to 16 mg·L-1.The geometric configuration of all the compounds was op-timized by employing semiempirical quantum chemical method(Gaussian03,AM1).In this way,quantum chemistry and physical chemistry parameters was calculated,the primary study of quantitative structure activity relationship to Bacillus subtilis showed the MIC50of the compounds with electron donating group is related to ELUMO、EL-H、LS-N、QNand D,and the MIC50of the compounds with electron-withdrawing group is related to the volume of molecule.%以1,2-苯并异噻唑啉-3-酮,取代苯胺和甲醛为原料一步法合成11个曼尼希碱类苯并异噻唑啉酮类衍生物.选取枯草芽孢杆菌、金黄色葡萄球菌、白色葡萄球菌、大肠杆菌、肺炎克雷伯菌和绿脓杆菌对化合物进行初步抑菌活性测试,结果表明合成化合物除对绿脓杆菌抑制效果稍差外,对其余测试菌种有非常好的生长抑制活性,MIC50介于4~16mg·mL-1.采用Gaussian03半经验计算方法AM1对分子几何构型进行全优化,计算得到量子化学参数和物理化学参数,针对枯草芽孢杆菌进行构效关系研究,结果表明当取代基为供电子取代基时,摩尔浓度的MIC50值和最低空轨道能级ELUMO、EL-H、LS-N、QN以及二面角D相关性显著,当取代基为氯、溴、硝基等吸电子取代基团时,摩尔浓度的MIC50值和分子体积显著相关.