title: Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor (VDR) agonistic activity based on the diphenylpentane skeleton.
abstract: Vitamin D receptor (VDR) is a family of nuclear receptors (NR) that regulates physiological effects such as the immune system, calcium homeostasis, and cell proliferation. We synthesized non-secosteroidal VDR ligands bearing a long alkyl chain based on the diphenylpentane skeleton. The VDR-mediated transcriptional activities of the synthesized compounds were evaluated using a reporter gene assay and HL-60 cell differentiation-inducing assay. We herein described the structure-activity relationship and effects of alkyl-chain length on VDR-mediated transcriptional activity.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Yorioka
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Noguchi-Yachide
authors.affiliation: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Ohoka
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kurashima-Kinoshita
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Motoyoshi
authors.affiliation: Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Nojiri
authors.affiliation: Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.affiliation: School of Medicine, Nihon University, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
authors.affiliation: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: masaaki@nihs.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
mesh_terms: D000478:Alkylation; D001681:Biological Assay; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010420:Pentanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008024:Ligands; D010420:Pentanes; D018167:Receptors, Calcitriol
keywords: Long alkyl chain; Non-secosteroidal VDR ligands; Vitamin D receptor