1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation

Gary H. Posner, Kathryn Z. Guyton, Thomas W. Kensler, Julia Barsony, Mara E. Lieberman, G. Satyanarayana Reddy, Jeffrey W. Clark, Khursheed F. Wankadiya, Kou Ti Tserng

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Abstract

1α-Hydroxymethyl-25-hydroxyvitamin D3 homology (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. 1α-Hydroxymethyl-25-hydroxyvitamin D3 homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes.

Original languageEnglish (US)
Pages (from-to)1835-1840
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume3
Issue number9
DOIs
StatePublished - Sep 1993

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ASJC Scopus subject areas

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

Cite this

Posner, G. H., Guyton, K. Z., Kensler, T. W., Barsony, J., Lieberman, M. E., Reddy, G. S., Clark, J. W., Wankadiya, K. F., & Tserng, K. T. (1993). 1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation. Bioorganic and Medicinal Chemistry Letters, 3(9), 1835-1840. https://doi.org/10.1016/S0960-894X(00)80115-8