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依据酶过渡态理论,通过量子化学计算实验对磺胺类药物抑菌机制进行了尝试性的探讨.发现对氨基苯磺酰胺与二氢蝶酸反应的过渡态确实相似于对氨基苯甲酸与二氢蝶酸反应的过渡态结构,从而可以竞争性抑制二氢蝶酸合成酶的催化作用.计算结果能够更深刻地解释对氨基苯磺酰胺N原子上进行取代的必要性和磺酰胺结构片段的构效关系.另外,本文猜想磺胺类药物产生杀菌作用更重要的原因可能是其本身代谢产物对催化下游反应的叶酰聚谷氨酸合成酶的直接抑制作用.
According to the theory of enzymatic transition state, the mechanism of bacteriostasis of sulfonamides was explored by quantum chemistry calculation experiment.It was found that the transition state between p-aminobenzenesulfonamide and dihydropteric acid was indeed similar to that of p-aminobenzoic acid and dihydro The transition state structure of the pteroic acid reaction so that it can competitively inhibit the catalysis of the dihydropteroic acid synthase.The calculation results provide a more profound explanation of the necessity of substitution on the p-aminobenzenesulfonamide N atom and the structure of the sulfonamide structure fragment In addition, this article speculated that the bactericidal effect of sulfa drugs may be more important because of its own metabolites to catalyze the downstream reaction of folic acid polyglutamate synthase direct inhibition.