@article{APS3741,
author = {Yu-chian Chen and Kun-tze Chen},
title = {Novel selective inhibitors of hydroxyxanthone derivatives for human cyclooxygenase-2},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {12},
year = {2016},
keywords = {},
abstract = {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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3741}
}