磷脂酶A_2吲哚类抑制剂的结构和活性关系

Structure-Affinity Relationship of Indole-Based Inhibitors for Phospholipase A_2

应用一种新的预测酶-配体复合物亲和性的方法来研究磷脂酶A2蚓哚类抑制剂的结构-活性关系．磷脂酶A2-抑制剂复合物的三维结构是用分子模构的方法搭建的，复合物的亲和性由程序SCORE计算．共分析了12个抑制剂分子．计算所得的亲和性和实验测定值吻合得很好，明显优于用CoMFA方法分析同一系列化合物所给出的结果．通过分析SCORE的输出结果，识别出了蚓哚类抑制剂和磷脂酶A2相互作用的关键位点，为设计新型的磷脂酶A2抑制剂提供了指导．

A new method which can estimate the binding affinity of an enzyme-ligand complexwas apphed to studying the indole-based inhibitors for human synovial fluid phospholipase A2.The three-dimetisional structures of phospholipase-inhibitor complexes were modeled by molecular docking and energy mmmmization The bindmg affnities were calculated by program SCORE. Alltogether 12 mhibitors were analyzed .The calc The calculated IC50 values fit well with the experimentallyobserved values By contrast, CoMFA studies of the salne series of inhibitors yielded nmch poorerresulets. From SCORE's output, the pharmacophorc of phospholipase A2 inhibitors was also derived, which is valuable for designing novel inhibitors.