Molecular docking and 3-D QSAR studies of substituted 2,2-bisaryl-bicycloheptanes as human 5-Lipoxygenase-Activating Protein (FLAP) inhibitors

作者：Ma Xiang^*; Zhou Lu; Zuo Zhi Li; Liu Jian; Yang Min; Wang Rong Wei

来源：QSAR and Combinatorial Science, 2008, 27(9): 1083-1091.

DOI：10.1002/qsar.200810053

• CoMFA
• 3-D QSAR
• 5-Lipoxygenase-Activating Protein (FLAP)
• molecular docking
• substituted 2,2-bisaryl-bicycloheptanes

Leukotrienes have been shown to be involved in a variety of diseases such as cardiovascular diseases, cancer, asthma, ulcerative colitis, and rhinitis. 5-Lipoxygenase-Activating Protein (FLAP) was found to be a key enzyme of leukotriene synthesis. Comparative Molecular Field Analysis (CoMFA) and molecular docking studies were carried out on a series of substituted 2,2-bisaryl-bicycloheptanes FLAP inhibitors. The docking results provided a reliable conformational alignment scheme for 3-D QSAR model. Based on the docking conformations, highly predictive CoMFA model was performed with a leave-one-out cross-validated q(2) of 0.651. The noncross-validated analysis with four optimum components revealed a conventional r(2) value of 0.972, F= 175.674, and an estimated standard error of 0.169. the predictive ability of this model was validated by the testing set with a conventional r(2) value of 0.920. The analyses may be used to design more potent FLAP inhibitors and predict their activities prior to synthesis.

• 出版日期2008-9
• 单位四川大学