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.
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This project was supported by grants from the National Science Council of China (NSC 94-2213-E-039-002) and China Medical University (CMU95-033, CMU95-156, and CMU95-239).
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Chen, Yc., Chen, Kt. Novel selective inhibitors of hydroxyxanthone derivatives for human cyclooxygenase-2. Acta Pharmacol Sin 28, 2027–2032 (2007). https://doi.org/10.1111/j.1745-7254.2007.00663.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00663.x
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