The potential role of the 5,6-dihydropyridin-2(1H)-one unit of piperlongumine on the anticancer activity |
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Authors: | Wen-Wen Mu Peng-Xiao Li Yue Liu Jie Yang Guo-Yun Liu |
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Institution: | School of Pharmacy, Liaocheng University, 1 Hunan Street, Liaocheng Shandong 252000 China, +86 15063505132 |
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Abstract: | Piperlongumine (PL), a potent anticancer agent from the plant long pepper (Piper longum), contains the 5,6-dihydropyridin-2(1H)-one heterocyclic scaffold and cinnamoyl unit. In this paper, we synthesized a series of PL analogs and evaluated their cytotoxicity against cancer cells for the sake of exploring which pharmacophore plays a more potent role in enhancing the anticancer activities of PL. These results illustrated that the position effect, not the electronic effect, of substituents plays a certain role in the cytotoxicity of PL and its analogs. More important, the 5,6-dihydropyridin-2(1H)-one unit, a potent pharmacophore in enhancing the antiproliferative activities of PL, could react with cysteamine and lead to ROS generation, and then bring about the occurrence of ROS-induced downstream events, followed by cell cycle arrest and apoptosis. This work suggests that introducing a lactam unit containing Michael acceptors may be a potent strategy to enhancing the anticancer activity of drugs.Piperlongumine (PL) could induce A549 cells apoptosis through ROS-mediated pathway and the 5,6-dihydropyridin-2-(1H)-one unit is crucial for its anticancer activity. |
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