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目的:寻找COX/5-LO双重抑制剂的生物活性与化学结构之间的关系,为设计合成新型COX/5-LO双重抑制剂提供理论依据。方法:选择16个活性较强的COX/5-LO双重抑制剂,利用CNDO/2程序进行化合物的量子化学参数计算以及定量构效关系研究。结果:这些化合物对5-LO的抑制作用主要与LUMO和HOMO本征值之差以及分子偶极矩呈正相关;抑制COX作用主要与电子总能量呈负相关,与分子总能量和分子偶极矩呈正相关。结论:增加分子偶极矩,有可能同时增强COX/5-LO双重抑制作用,从而得到高效低毒的非甾体抗炎药。
OBJECTIVE: To find out the relationship between the biological activity and chemical structure of COX / 5-LO dual inhibitors, and to provide a theoretical basis for the design of a new dual COX / 5-LO inhibitor. METHODS: Sixteen highly active COX / 5-LO inhibitors were selected and the quantum chemical parameters of the compounds were calculated and the QSAR studies were performed using the CNDO / 2 program. Results: The inhibitory effect of these compounds on 5-LO was mainly related to the difference between eigenvalues of LUMO and HOMO and the dipole moments of molecules. The inhibition of COX was mainly negatively correlated with the total energy of the electrons and the total energy and molecular dipole moment Was positively correlated. Conclusion: Increasing the molecular dipole moment may enhance the dual inhibition of COX / 5-LO at the same time, so that a highly effective and low toxicity nonsteroidal anti-inflammatory drug can be obtained.