Synthesis of New Vitamin K Analogues as Steroid and Xenobiotic Receptor (SXR) Agonists: Insights into the Biological Role of the Side Chain Part of Vitamin K

Vitamin K(2) has been demonstrated to induce gene expression related to bone formation through a nuclear steroid and xenobiotic receptor (SXR). We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and evaluated the transcriptional activity of the target gene. The transcriptional activity was related to the length of the side chain which allowed optimal interaction with ligand-binding domain of SXR.