Sakane Rie, Kimura Kimito, Hirota Yoshihisa, Ishizawa Michiyasu, Takagi Yuta, Wada Akimori, Kuwahara Shigefumi, Makishima Makoto, Suhara Yoshitomo
Laboratory of Organic Synthesis and Medicinal Chemistry, Faculty of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
Laboratory of Biochemistry, Faculty of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan.
Bioorg Med Chem Lett. 2017 Nov 1;27(21):4881-4884. doi: 10.1016/j.bmcl.2017.09.038. Epub 2017 Sep 18.
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.
维生素K是γ-谷氨酰羧化酶的必需辅因子，与血液凝固和骨骼形成有关。维生素K同系物之一的甲萘醌-4在体内生物合成，具有多种生物活性，如作为类固醇和外源性受体的配体、保护神经元细胞免受氧化应激等。基于此背景，我们关注甲萘醌在祖细胞向神经元细胞分化活性中的作用，并合成了具有ω-末端侧链修饰的新型维生素K衍生物。我们在此报告了新型维生素K类似物，其在ω-末端侧链引入了烷基化苯基。与对照相比，这些化合物表现出强大的分化活性。
