Structure–Activity Relationship of Novel Menaquinone-4 Analogues: Modification of the Side Chain Affects their Biological Activities

We synthesized new vitamin K analogues with demethylation or reduction of the double bonds of the side chain of menaquinone-4 (MK-4) and evaluated their SXR-mediated transcriptional activity as well as the extent of their conversion to MK-4. The results indicated that the analogue with the methyl group deleted at the 7′ site of the side chain part affected conversion activity to MK-4. In contrast, a decrease in the number of the double bonds in the side chain moiety appeared to decrease the SXR-mediated transcriptional activity

Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells

We synthesized new vitamin K₂ analogues with ω-terminal modifications of the side chain and evaluated their selective differentiation of neuronal progenitor cells into neurons in vitro. The result of the assay showed that the menaquinone-3 analogue modified with the <i>m</i>-methylphenyl group had the most potent activity, which was twice as great as the control. This finding indicated that it is possible to obtain much more potent compounds with modification of the structure of vitamin K₂

Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells

We synthesized new vitamin K₂ analogues with ω-terminal modifications of the side chain and evaluated their selective differentiation of neuronal progenitor cells into neurons in vitro. The result of the assay showed that the menaquinone-3 analogue modified with the <i>m</i>-methylphenyl group had the most potent activity, which was twice as great as the control. This finding indicated that it is possible to obtain much more potent compounds with modification of the structure of vitamin K₂