Novel selective inhibitors of hydroxyxanthone derivatives for human cyclooxygenase-2

被引:30
作者
Chen, Yu-chian [1 ]
Chen, Kun-tze [1 ]
机构
[1] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan
关键词
cyclooxygenase; non-steroidal anti-inflammatory drugs; xanthone; molecular simulation; interaction energy; inhibitors;
D O I
10.1111/j.1745-7254.2007.00663.x
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aim: To screen the selective inhibitors for human cyclooxygenase-2 ((h)COX-2) utilizing molecular simulation. Methods: Eight xanthone derivatives, compounds A-H, were employed by the structure-based research methodology. Resveratrol and NS-398 were selected as the control compounds for COX-1 and COX-2, respectively. The docking results were scored and the interaction energies of the complexes were calculated by CHARMm forcefield. Results: NS-398 could not dock into the active site of COX-1. However, resveratrol, the specific selective compound for COX-1, gained lower interaction energy while docked in COX-1. The lower interaction energies were investigated, while compound B and F were docked into the catalytic sites of COX-1 and COX-2, respectively. Compound A, 1,3,6,7-tetrahydroxyxanthone, revealed high inhibitory potency to both COX-1 and COX-2. Conclusion: The conformations of the docking would influence the values of interaction energies. The hydrogen bond could also increase the stability of the whole complex, which might suggest that compound B had a suitable conformation in the tunnel-like active site of COX-1. Compound F, a potent agent for COX-2, revealed a strong hydrogen bond with Ser516 in human COX-2 to form a stable complex.
引用
收藏
页码:2027 / 2032
页数:6
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