Coats E A, Seydel J K, Wiese M
Division of Pharmacology and Medicinal Chemistry, College of Pharmacy, University of Cincinnati, OH 45267-0004.
J Enzyme Inhib. 1987;1(4):259-66. doi: 10.3109/14756368709020123.
Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N1-phenylsulfonilamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pKa irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N1-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.
在存在和不存在协同浓度甲氧苄啶的情况下，对一系列4-取代-N1-苯基磺酰胺进行了测试，以确定其对大肠杆菌细胞培养物的生长抑制作用。通过回归分析建立的定量构效关系表明，无论是否存在甲氧苄啶，细菌生长抑制对磺酰胺pKa的依赖性都是相同的。在存在或不存在4-二甲基氨基-N1-苯基磺胺的情况下，对一小系列苄基嘧啶进行检测，也得到了类似的结果。由于增效剂的存在并未改变构效关系，因此可以得出结论，磺酰胺与苄基嘧啶之间不存在直接相互作用，观察到的协同作用仅仅是叶酸生物合成途径顺序阻断的动力学结果。
