Synthesis and Biological Activity of 1α,2α,25-Trihydroxyvitamin D₃ : Active Metabolite of 2α-(3-Hydroxypropoxy)-1α,25-dihydroxyvitamin D₃ by Human CYP3A4 Synthesis and Biological Activity of 1α,2α,25-Trihydroxyvitamin D<sub>3</sub>: Active Metabolite of 2α-(3-Hydroxypropoxy)-1α,25-dihydroxyvitamin D<sub>3</sub> by Human CYP3A4

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Author(s)

Abstract

Our previous studies revealed that recombinant human CYP3A4 converted 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D<sub>3</sub> (O2C3), which was a more potent binder to vitamin D receptor (VDR) than the natural hormone, 1α,25-dihydroxyvitamin D<sub>3</sub> (1α,25(OH)<sub>2</sub>D<sub>3</sub>, <b>1</b>), to 1α,2α,25-trihydroxyvitamin D<sub>3</sub> (<b>2</b>). Here, we synthesized <b>2</b> using the Trost Pd-mediated coupling reaction between an A-ring precursor and a CD-ring bromoolefin and evaluated its preliminary biological activity. We found that metabolite <b>2</b> from O2C3 was still active as a VDR ligand while maintaining human VDR binding affinity (27.3% of 1α,25(OH)<sub>2</sub>D<sub>3</sub>) and HL-60 cell differentiation activity (62% of 1α,25(OH)<sub>2</sub>D<sub>3</sub>).

Journal

  • Chemical and Pharmaceutical Bulletin

    Chemical and Pharmaceutical Bulletin 62(2), 182-184, 2014

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130003390755
  • NII NACSIS-CAT ID (NCID)
    AA00602100
  • Text Lang
    ENG
  • ISSN
    0009-2363
  • NDL Article ID
    025171846
  • NDL Call No.
    Z53-D167
  • Data Source
    NDL  J-STAGE 
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