title: Synthesis of novel vitamin K2 analogues with modification at the ω-terminal position and their biological evaluation as potent steroid and xenobiotic receptor (SXR) agonists.
abstract: Vitamin K(2) is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K(2) analogues with hydroxyl or phenyl groups at the ω-terminal of the side chain. The up-regulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the ω-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.
authors.affiliation: Laboratory of Environmental Sciences, Yokohama College of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Suhara
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kimie
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Akimori
authors.initials: A
authors.lastname: Wada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008958:Models, Molecular; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000819:agonists*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D008024:Ligands; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D024482:Vitamin K 2; D008156:Luciferases