Synthesis of C6-epimer derivatives of diacetoxy acetal derivative of santonin and their inducing effects on HL-60 leukemia cell differentiation

Sin Ho Kweon, Keun Tae Kim, Joon Hee Hong, Tae Sung Kim, Bo Gil Choi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Induction of differentiation is a new and promising approach to leukemia therapy, well illustrated by the treatment of acute promyelocytic leukemia with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combination of either 1,25-(OH) 2D3 or ATRA and chemotherapy, adverse effects 1,25-(OH)2D3 or ATRA such as hypercalcemic effects have decreased, and long-term survival has improved. In a previous study, we demonstrated that santonin could be chemically modified into a diacetoxy acetal derivative of santonin with strong differentiation-inducing activity. In this study, we further synthesized C6-epimer derivatives of diacetoxy acetal derivative of santonin and tested their effects on HL-60 cell differentiation. Some of the C6-epimer derivatives themselves induced increases in cell differentiation. Especially, (11S)-3,3-(ethylenedioxy) eudesmano-13-ol-6β-acetate (7) was demonstrated to induce differentiation with larger than 80% of the cells attaining a differentiated phenotype. Importantly, 7 strongly enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either low doses of 1,25-(OH) 2D3 or ATRA. The ability to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA by 7 may improve outcomes in the therapy of acute promyelocytic leukemia.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalArchives of pharmacal research
Volume34
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Keywords

  • 1,25-dihydroxyvitamin D
  • 6-Epimer
  • All-trans retinoic acid
  • DAAS
  • Differentiation
  • Leukemia

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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