Deuteration of the Farnesyl Terminal Methyl Groups of δ-Tocotrienol and Its Effects on the Metabolic Stability and Ability of Inducing G-CSF Production

Xingui Liu, Zhengya Gao, Qiang Fu, Lin Song, Peiyi Zhang, Xuan Zhang, Howard Hendrickson, Peter A Crooks, Daohong Zhou, Guangrong Zheng

Abstract

δ-tocotrienol (DT3), a member of vitamin E family, has been shown to have a potent radio-protective effect. However, its application as a radioprotectant is limited, at least in part, by its short plasma elimination half-life and low bioavailability. In an effort to increase the metabolic stability of DT3, a deuterium substituted DT3 derivative, d6-DT3, was designed and synthesized. d6-DT3 showed improved in vitro and in vivo metabolic stability compared to DT3. The unexpected lower potency of d6-DT3 in inducing granulocyte-colony stimulating factor (G-CSF) production in mouse revealed that the metabolite(s) of DT3 might play a major role in inducing G-CSF induction.

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