Deuteration of the farnesyl terminal methyl groups of δ-tocotrienol and its effects on the metabolic stability and ability of inducing G-CSF production

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.