Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor (VDR) agonistic activity based on the diphenylpentane skeleton

Takashi Misawa; Momoko Yorioka; Yosuke Demizu; Tomomi Noguchi-Yachide; Nobumichi Ohoka; Megumi Kurashima-Kinoshita; Hitomi Motoyoshi; Hisao Nojiri; Atsushi Kittaka; Makoto Makishima; Mikihiko Naito; Masaaki Kurihara

doi:10.1016/j.bmcl.2015.09.030

Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor (VDR) agonistic activity based on the diphenylpentane skeleton

Bioorg Med Chem Lett. 2015 Nov 15;25(22):5362-6. doi: 10.1016/j.bmcl.2015.09.030. Epub 2015 Sep 12.

Affiliations

¹ Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
² Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
³ Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
⁴ Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
⁵ School of Medicine, Nihon University, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
⁶ 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: [email protected].

PMID: 26432035
DOI: 10.1016/j.bmcl.2015.09.030

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.

Keywords: Long alkyl chain; Non-secosteroidal VDR ligands; Vitamin D receptor.

MeSH terms

Alkylation
Biological Assay
Cell Differentiation / drug effects
HL-60 Cells
Humans
Hydrophobic and Hydrophilic Interactions
Ligands
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Pentanes / chemical synthesis
Pentanes / chemistry*
Pentanes / pharmacology
Receptors, Calcitriol / agonists*
Receptors, Calcitriol / chemistry
Receptors, Calcitriol / genetics
Structure-Activity Relationship
Transcription, Genetic / drug effects

Substances

Ligands
Pentanes
Receptors, Calcitriol