Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells

Kimito Kimura; Yoshihisa Hirota; Shigefumi Kuwahara; Atsuko Takeuchi; Chisato Tode; Akimori Wada; Naomi Osakabe; Yoshitomo Suhara

doi:10.1021/acs.jmedchem.6b01717

Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells

J Med Chem. 2017 Mar 23;60(6):2591-2596. doi: 10.1021/acs.jmedchem.6b01717. Epub 2017 Mar 3.

Authors

Kimito Kimura¹, Yoshihisa Hirota², Shigefumi Kuwahara³, Atsuko Takeuchi⁴, Chisato Tode⁴, Akimori Wada⁵, Naomi Osakabe⁶, Yoshitomo Suhara¹

Affiliations

¹ Laboratory of Organic Synthesis and Medicinal Chemistry, Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology , 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
² Laboratory of Biochemistry, Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology , 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
³ Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University , 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, 981-8555, Japan.
⁴ Analytical Laboratory, Kobe Pharmaceutical University , 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
⁵ Department of Life Science for Organic Chemistry, Kobe Pharmaceutical University , 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
⁶ Food and Nutrition Laboratory, Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology , 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.

PMID: 28225275
DOI: 10.1021/acs.jmedchem.6b01717

Abstract

We synthesized novel vitamin K₂ analogues that incorporated a heteroatom and an aromatic ring in the side chain and evaluated their effect on the selective differentiation of neuronal progenitor cells into neurons in vitro. The results showed that a menaquinone-2 analogue bearing a p-fluoroaniline had the most potent activity, which was more than twice as great as the control. In addition, the neuronal selectivity was more than 3 times greater than the control.

Publication types

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

MeSH terms

Aniline Compounds / chemistry
Aniline Compounds / pharmacology
Animals
Cells, Cultured
Female
Mice
Mice, Inbred C57BL
Neural Stem Cells / cytology
Neural Stem Cells / drug effects*
Neurogenesis / drug effects*
Vitamin K / analogs & derivatives*
Vitamin K / pharmacology*
Vitamin K 2 / analogs & derivatives
Vitamin K 2 / chemistry
Vitamin K 2 / pharmacology
Vitamins / chemistry*
Vitamins / pharmacology*

Substances

Aniline Compounds
Vitamins
Vitamin K 2
Vitamin K
menatetrenone
2-fluoroaniline