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 gr...

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Veröffentlicht in:	Journal of medicinal chemistry 2012-02, Vol.55 (4), p.1553-1558
Hauptverfasser:	Suhara, Yoshitomo, Hanada, Norika, Okitsu, Takashi, Sakai, Miho, Watanabe, Masato, Nakagawa, Kimie, Wada, Akimori, Takeda, Kazuyoshi, Takahashi, Kazuhiko, Tokiwa, Hiroaki, Okano, Toshio
Format:	Artikel
Sprache:	eng
Schlagworte:	Cell Line, Tumor Deuterium Genes, Reporter Humans Luciferases - biosynthesis Luciferases - genetics Protein Binding Protein Multimerization Receptors, Steroid - genetics Receptors, Steroid - metabolism Retinoid X Receptors - metabolism Structure-Activity Relationship Transcription, Genetic - drug effects Vitamin K 2 - analogs & derivatives Vitamin K 2 - chemical synthesis Vitamin K 2 - chemistry Vitamin K 2 - pharmacology
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Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm2013166