Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

Masashi Takano, Erika Higuchi, Kazunari Higashi, Keisuke Hirano, Akiko Takeuchi, Daisuke Sawada, Atsushi Kittaka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D3: ca. 15% of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).

Original languageEnglish
Pages (from-to)1274-1287
Number of pages14
JournalHeterocycles
Volume90
Issue number2
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Calcitriol Receptors
Calcitriol
Transcriptional Activation
Assays
Osteosarcoma
Luciferases
Human Activities
Binders
1,25-dihydroxy-19-norvitamin D3

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3. / Takano, Masashi; Higuchi, Erika; Higashi, Kazunari; Hirano, Keisuke; Takeuchi, Akiko; Sawada, Daisuke; Kittaka, Atsushi.

In: Heterocycles, Vol. 90, No. 2, 2015, p. 1274-1287.

Research output: Contribution to journalArticle

Takano, M, Higuchi, E, Higashi, K, Hirano, K, Takeuchi, A, Sawada, D & Kittaka, A 2015, 'Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3', Heterocycles, vol. 90, no. 2, pp. 1274-1287. https://doi.org/10.3987/COM-14-S(K)108
Takano, Masashi ; Higuchi, Erika ; Higashi, Kazunari ; Hirano, Keisuke ; Takeuchi, Akiko ; Sawada, Daisuke ; Kittaka, Atsushi. / Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3. In: Heterocycles. 2015 ; Vol. 90, No. 2. pp. 1274-1287.
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abstract = "Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6{\%} of 1α,25-dihydroxyvitamin D3: ca. 15{\%} of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).",
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