'Novel alkyl side chain sulfone 1α,25-dihydroxyvitamin D3 analogs: A comparison of in vitro antiproliferative activities and in vivo calcemic activities'

Aimee R. Usera, Patrick Dolan, Thomas W. Kensler, Gary H. Posner

Research output: Contribution to journalArticle

Abstract

The replacement of a t-butyl group with a trifluoromethyl group has profound effects on the biological profile of 1α,25-dihydroxyvitamin D3 sulfone analogs. Investigation of whether the improved biological activities are due to steric and electronic factors of the trifluoromethyl group led to the design, synthesis and biological evaluation of two analogous alkyl sulfone molecules, methyl sulfone (AU-16-ene-25-SO2-CH3) and isopropyl sulfone (AU-16-ene-25-SO2-i-Pr). These alkyl sulfones are sterically comparable to, but electronically very different from a trifluoromethyl group. The syntheses, antiproliferative activities and calcemic activities of these new alkyl sulfones are presented herein. In comparing the in vitro antiproliferative profiles of the new alkyl sulfone 1α,25-dihydroxyvitamin D3 analogs with the trifluoromethylsulfone and an analogous t-butyl sulfone, the activities increase in the following order: CH3<t-Bu≅i-Pr<CF3. In contrast to the calcemic t-butyl sulfone, the novel alkyl sulfones and trifluoromethyl sulfone display desirable low calcemic levels.

Original languageEnglish (US)
Pages (from-to)5627-5631
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number15
DOIs
StatePublished - Aug 1 2009

Keywords

  • 1α,25-Dihydroxyvitamin D
  • Antiproliferative
  • Calcitriol
  • Sulfone
  • Trifluoromethyl

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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