【摘 要】
：
COX-2 has long been exploited in the treatment of inflammation and relief of pain; however,research increasingly suggests COX-2 inhibitors might possess pot
【机 构】
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StateKeyLaboratoryofPharmaceuticalBiotechnology,NanjingUniversity,Nanjing210046,People'sRepublicofC
【出 处】
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第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)
论文部分内容阅读
COX-2 has long been exploited in the treatment of inflammation and relief of pain; however,research increasingly suggests COX-2 inhibitors might possess potential benefits to thwart tumour processes.In the present study,we designed a series of novel COX-2 inhibitors based on analysis of known inhibitors combined with an in silico scaffold modification strategy.A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound,which was then substituted,synthesized and evaluated by a variety of bioassays.Derivative 4d was identified as a potent COX-2 enzyme inhibitor and exerted an anticancer effect through COX-2 inhibition.Further investigation confirmed that 4d could induce A549 cell apoptosis and arrest the cell cycle at the G2/M phase.Moreover,treatment with 4d reduced A549 cell adhesive ability and COX-2 expression.The morphological variation of treated cells was also visualized by confocal microscopy.Overall,the biological profile of 4d suggests that this compound may be developed as a potential anticancer agent.
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