C15-functionalized 16-Ene-1α,25-dihydroxyvitamin D 3 is a new vitamin D analog with unique biological properties

Go Kumagai, Masashi Takano, Kanako Shindo, Daisuke Sawada, Nozomi Saito, Hiroshi Saito, Shinji Kakuda, Ken Ichiro Takagi, Midori Takimoto-Kamimura, Kazuya Takenouchi, Tai C. Chen, Atsushi Kittaka

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The Δ 16 structure as a vitamin D analog enhanced vitamin D receptor (VDR) binding affinity and induced significant cell differentiation, whereas its relative calcemic activity was reduced compared to 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2D 3). Methodologies available to introduce a double bond at C16-C17 of the D-ring on the seco-steroidal skeleton were limited; therefore, a new synthetic strategy was developed to obtain not only the Δ 16 structure, but also a new C15-functional group. Since C15-functionalization was unprecedented in vitamin D analog studies, the hybrid structure of Δ 16 and the C15-OH group at the D-ring may provide important information on the structure-activity relationship with vitamin D analogs. The synthesized 16-ene-2α-methyl-1α,15α,25-trihydroxyvitamin D 3 showed almost 3-times higher VDR binding affinity and an equipotent level of osteocalcin promoter transactivation activity in human osteosarcoma cells as compared to 1α,25(OH) 2D 3.

Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalAnticancer research
Volume32
Issue number1 PART 2
Publication statusPublished - Jan 1 2012
Externally publishedYes

Keywords

  • 15-substituted vitamin D
  • 16-ene-vitamin D
  • S 2′ reaction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kumagai, G., Takano, M., Shindo, K., Sawada, D., Saito, N., Saito, H., Kakuda, S., Takagi, K. I., Takimoto-Kamimura, M., Takenouchi, K., Chen, T. C., & Kittaka, A. (2012). C15-functionalized 16-Ene-1α,25-dihydroxyvitamin D 3 is a new vitamin D analog with unique biological properties. Anticancer research, 32(1 PART 2), 311-317.