Systematic synthesis and anti-inflammatory activity of ω-carboxylated menaquinone derivatives--Investigations on identified and putative vitamin K₂ metabolites

Shinya Fujii; Akitaka Shimizu; Noriaki Takeda; Kazuki Oguchi; Tomoko Katsurai; Hitoshi Shirakawa; Michio Komai; Hiroyuki Kagechika

doi:10.1016/j.bmc.2015.03.070

Systematic synthesis and anti-inflammatory activity of ω-carboxylated menaquinone derivatives--Investigations on identified and putative vitamin K₂ metabolites

Bioorg Med Chem. 2015 May 15;23(10):2344-52. doi: 10.1016/j.bmc.2015.03.070. Epub 2015 Apr 4.

Authors

Shinya Fujii¹, Akitaka Shimizu², Noriaki Takeda², Kazuki Oguchi³, Tomoko Katsurai³, Hitoshi Shirakawa³, Michio Komai³, Hiroyuki Kagechika⁴

Affiliations

¹ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032 Tokyo, Japan.
² Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
³ Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
⁴ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address: kage.chem@tmd.ac.jp.

PMID: 25858455
DOI: 10.1016/j.bmc.2015.03.070

Abstract

Vitamin K is an essential nutrient for blood coagulation and bone homeostasis, and also functions in many physiological processes including inflammation and cancer progression. However, the nature and activities of its metabolites remain unclear. We report here systematic synthesis of ω-carboxylated derivatives of menaquinone (vitamin K2), including previously identified metabolites 5, K acid I (10), and K acid II (12), and evaluation of their inhibitory activity toward LPS-stimulated induction of inflammatory cytokines. These results should contribute to an improved understanding of the biochemistry and pharmacology of vitamin K.

Keywords: Anti-inflammatory activity; Menaquinone; Metabolite; Vitamin K.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis*
Anti-Inflammatory Agents / pharmacology
Biotransformation
Carboxylic Acids / chemistry*
Inflammation / prevention & control
Interleukin-1beta / antagonists & inhibitors
Interleukin-1beta / biosynthesis
Interleukin-6 / antagonists & inhibitors
Interleukin-6 / biosynthesis
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Macrophages / cytology
Macrophages / drug effects
Macrophages / immunology
Mice
Naphthalenes / chemistry
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Tumor Necrosis Factor-alpha / biosynthesis
Vitamin K 2 / analogs & derivatives*
Vitamin K 2 / chemical synthesis*
Vitamin K 2 / pharmacology

Substances

Anti-Inflammatory Agents
Carboxylic Acids
Interleukin-1beta
Interleukin-6
Lipopolysaccharides
Naphthalenes
Tumor Necrosis Factor-alpha
interleukin-6, mouse
Vitamin K 2