- Identification of novel ROS inducers: Quinone derivatives tethered to long hydrocarbon chains
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We performed the first synthesis of the 17-carbon chain-tethered quinone moiety 22 (SAN5201) of irisferin A, a natural product exhibiting anticancer activity, and its derivatives. We found that 22 is a potent ROS inducer and cytotoxic agent. Compound 25 (SAN7401), the hydroquinone form of 22, induced a significant release of intracellular ROS and apoptosis (EC50 = 1.3-2.6 μM) in cancer cell lines, including A549 and HCT-116. Compared with the activity of a well-known ROS inducer, piperlongumine, 22 and 25 showed stronger cytotoxicity and higher selectivity over noncancerous cells. Another hydroquinone tethering 12-carbon chain, 26 (SAN4601), generated reduced levels of ROS but showed more potent cytotoxicity (EC50 = 0.8-1.6 μM) in cancer cells, although it lacked selectivity over noncancerous cells, implying that the naturally occurring 17-carbon chain is also crucial for ROS production and a selective anticancer effect. Both 25 and 26 displayed strong, equipotent activities against vemurafenib-resistant SK-Mel2 melanoma cells and p53-deficient H1299 lung cancer cells as well, demonstrating their broad therapeutic potential as anticancer agents.
- Hong, Yeonsun,Sengupta, Sandip,Hur, Wooyoung,Sim, Taebo
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p. 3739 - 3750
(2015/05/27)
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- Naturally occurring 5-lipoxygenase inhibitor. II. Structures and syntheses of ardisianones A and B, and maesanin, alkenyl-1,4-benzoquinones from the rhizome of Ardisia japonica
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New alkenyl-1,4-benzoquinones, ardisianones A (1) and B (2), and the known maesanin (3) as 5-lipoxygenase inhibitors have been isolated from the rhizome of Ardisia japonica. Their structures have been elucidated as 2-methoxy-6-[(Z)-10'-pentadecenyl]-1,4-benzoquinone and 5-hydroxy-2-methoxy-6-[(Z)-8'-tridecenyl]-1,4-benzoquinone, respectively, on the basis of spectroscopic data and chemical degradation. Ardisianone A (1), maesanin (3) and belamcandol A (7) have been synthesized starting from belamcandol B (6), readily prepared by Wittig reaction between 9-(2-tetrahydropyranyloxy)nonanal and 3,5-dimethoxybenzyltriphenylphosphonium bromide followed by selective demethylation with sodium thioethoxide.
- Fukuyama,Kiriyama,Okino,Kodama,Iwaki,Hosozawa,Matsui
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p. 561 - 565
(2007/10/02)
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- Structures of belamcandols A and B isolated from the seed of Belamcanda chinensis
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The structures of belamcandols A and B isolated from the seeds of Belamcanda chinensis have been assigned to 2,4-dimethoxy-6-((Z)-10'-pentadecenyl)phenol and 1-O-methyl-5-((Z)-10'-pentadecenyl)resorcinol, respectively, based on spectroscopic data and chemical degradation. Belamcandol A inhibits 5-lipoxygenase activity at IC50 0.60 μM.
- Fukuyama,Okino,Kodama
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p. 1877 - 1879
(2007/10/02)
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