Synthesis and screening of novel vitamin E derivatives for anticancer functions

α-TEA, RRR-α-tocopherol ether linked acetic acid, exhibits potent anticancer actions in vitro and in vivo; whereas, the parent molecule has no anticancer activity. In this study, we incorporated fluorine at the chroman head and/or ether linkage between the chroman head and phytyl tail of α-TEA as well as RRR-α-tocopherol to synthesize 6 vitamin E derivatives, and evaluated the anticancer actions in vitro for ability to induce cell death by apoptosis of human MCF-7 and MDA-MB-231 breast cancer cell lines and mouse mammary cancer cell line 66cl-4GFP. All derivatives, with the exception of compound 12, exhibited anticancer properties. The modified α-TEA ether-type phytyl group exhibited the highest pro-apoptotic activity in comparison with α-TEA as well as other vitamin E derivatives.

Graphical abstractSix novel vitamin E derivatives based on α-TEA and RRR-α-tocopherol were prepared and most exhibited anticancer properties. The modified α-TEA ether-type phytyl group exhibited the highest pro-apoptotic activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Six novel vitamin E derivatives were synthesized. ► Synthesized compounds were tested in various human cancer cell lines. ► 5 derivatives exhibited anticancer properties. ► The configuration of the 2-position does not affect the activity.