用AM1分子轨道方法对萘啶酸及其类似物进行了优化计算。结果发现该类药物的抗菌活性与C 3位的空间构象和静电势分布有着紧密的联系。C-3位羧基 (或其模拟物 )与C-4位酮基共面性、以及它和母核共面性对抗菌活性十分重要,C-3位两个氧原子 (或其模拟羧酸)周围较强的负静电势也是影响活性的重要因素。

Nalidixic acid and its analogues (with C-3 carboxyl group substituted by other groups) were optimized by molecular orbital AM1 method . The results showed that the biological activities are closely related to the steric conformation and distribution of electrostatic potential of carboxyl group: The coplanatity between the group of C-3 position and the parent nucleus and the coplanatity between the group of C-3 position and C-4 keto group are very important for biological activities. It is also important that the two oxygen atoms of C-3 carboxyl(or simulateing carboxylic acid) have strongly negative electrostatic potential at the plane of quinolone ring.