title: [Structure-activity relationship of novel vitamin K analogues as steroid and xenobiotic receptor (SXR) agonists].
abstract: Vitamin K2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. 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 vitamin K2 analogues with hydroxyl or phenyl groups at the ω-terminal of the side chain. The upregulation 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: Yokohama College of Pharmacy, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Suhara
authors.forename: Sayaka
authors.initials: S
authors.lastname: Motoyoshi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hirota
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sawada
authors.forename: Kimie
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tokiwa
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
mesh_terms: D006801:Humans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014812:Vitamin K / Q000031:analogs & derivatives / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015262:Xenobiotics; D014812:Vitamin K