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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.

SUBMITTER: Liu X

PROVIDER: S-EPMC7433030 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Liu Xingui X Gao Zhengya Z Fu Qiang Q Song Lin L Zhang Peiyi P Zhang Xuan X Hendrickson Howard H Crooks Peter A PA Zhou Daohong D Zheng Guangrong G

Bioorganic & medicinal chemistry 20200408 11

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, d<sub>6</sub>-DT3, was designed and synthesized. d<sub>6</sub>-DT3 showed improved in vitro and in vivo metabolic stability compared to DT3. The unexpec ...[more]

PMID: 32291146

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