The latest research has indicated that anti-tumor agents with COX-2 inhibitory activity may benefit their anti-tumor efficiency. A series of sclerotiorin derivatives have been synthesized and screened for their cytotoxic activity against human lung cancer cells A549, breast cancer cells MDA-MB-435 using the MTT method. Among them, compounds 3, 7, 12, 13, 15, 17 showed good cytotoxic activity with IC50 values of 6.39, 9.20, 9.76, 7.75, 9.08, and 8.18 μM, respectively. In addition, all compounds were tested in vitro the COX-2 inhibitory activity. The results disclosed compounds 7, 13, 25 and sclerotiorin showed moderate to good COX-2 inhibition with the inhibitory ratios of 58.7%, 51.1%, 66.1% and 56.1%, respectively. Notably, compound 3 displayed a comparable inhibition ratio (70.6%) to the positive control indomethacin (78.9%). Furthermore, molecular docking was used to rationalize the potential of the sclerotiorin derivatives as COX2 inhibitory agents by predicting their binding energy, binding modes and optimal orientation at the active site of the COX-2. Additionally, the structure-activity relationships (SARS) have been addressed.
