Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities

• Published in: Bioorganic & medicinal chemistry letters 2017-11, Vol.27 (21), p.4881-4884
• Main Authors: Sakane, Rie, Kimura, Kimito, Hirota, Yoshihisa, Ishizawa, Michiyasu, Takagi, Yuta, Wada, Akimori, Kuwahara, Shigefumi, Makishima, Makoto, Suhara, Yoshitomo
• Format: Article
• Language: English
• Subjects: Alkylation; Animals; Cell Differentiation - drug effects; Cells, Cultured; Menaquinone-4; Mice; Microscopy, Fluorescence; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neuronal cells; PC12 Cells; Rats; Structure-Activity Relationship; SXR; Transcriptional activity; Vitamin K; Vitamin K - analogs & derivatives; Vitamin K - chemical synthesis; Vitamin K - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.09.038

[Display omitted] Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control.