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

Deuteration of the farnesyl terminal methyl groups of δ-tocotrienol and its effects on the metabolic stability and ability of inducing G-CSF production.
Bioorg Med Chem. 2020 Apr 08;:115498
Authors: Liu X, Gao Z, Fu Q, Song L, Zhang P, Zhang X, Hendrickson H, Crooks PA, Zhou D, Zheng G
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.
PMID: 32291146 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - April 7, 2020 Category: Chemistry Authors: Liu X, Gao Z, Fu Q, Song L, Zhang P, Zhang X, Hendrickson H, Crooks PA, Zhou D, Zheng G Tags: Bioorg Med Chem Source Type: research