| 摘要: | Prostaglandin endoperoxide H synthase (PGHS, also referred to cyclooxygenase, COX), is the important target while decreasing the prostanoids synthesis by blocking the active site of the enzyme. Cyclooxygenase-2 (COX-2) is the enzyme which catalyst arachidonic acid to PGH2, one could be metabolized to various prostanoids. Nowadays, many clinical tumorigenesis have been reported relating COX-2. To inhibit the overexpression of COX-2 some cell carcinogenesis could be reduced. Some xanthone derivates show the potent cytotoxic effect against hepatoma, and eight of these derivates were employed in this investigate. Ten compounds for 3-Alkylaminopropoxy-9,10-anththraquinone derivatives were used. Arachidonic acid (AA), NS-398, LM-4108 and aspirin were considered as control set. Through molecular simulation, all the compounds were docked in the active and executed dynamic cascade performing subsequently. Compound 1-hydroxy-3-(2-hydroxy-3-(isopropylamino)propoxy)anthracene-9,10-dione gain the lowest binding energy, -147.85 kcal/mol, revealing the best stable status within all compounds concluding AA and commercial drugs. Compound 2-(3-(isopropylamino)propoxy)anthracene-9,10-dione had the least stable conformation having -61.33 kcal/mol of binding energy in the lobby. The derivative of xanthone, 2,3-dihydroxy-9H-xanthen-9-one, had the lowest binding energy, -99.29 kcal/mol, within its group. Compound B1 had the best stability in the result, so it might against arachidonic acid being a potent inhibitor. Finally, to design the more potent inhibitors through hydrophobicity and pharmacophore would be imperious. |
