Synthesis of C-6-Epimer Derivatives of Diacetoxy Acetal Derivative of Santonin and their Inducing Effects on HL-60 Leukemia Cell Differentiation
- Authors
- Kweon, Sin Ho; Kim, Keun Tae; Hong, Joon Hee; Kim, Tae Sung; Choi, Bo Gil
- Issue Date
- 2월-2011
- Publisher
- PHARMACEUTICAL SOC KOREA
- Keywords
- DAAS; 6-Epimer; Differentiation; Leukemia; 1,25-dihydroxyvitamin D-3; All-trans retinoic acid
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v.34, no.2, pp.191 - 198
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- ARCHIVES OF PHARMACAL RESEARCH
- Volume
- 34
- Number
- 2
- Start Page
- 191
- End Page
- 198
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/113102
- DOI
- 10.1007/s12272-011-0202-4
- ISSN
- 0253-6269
- 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 D-3 [1,25-(OH)(2)D-3] or all-trans retinoic acid (ATRA). Using combination of either 1,25-(OH)(2)D-3 or ATRA and chemotherapy, adverse effects 1,25-(OH)(2)D-3 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 C-6-epimer derivatives of diacetoxy acetal derivative of santonin and tested their effects on HL-60 cell differentiation. Some of the C-6-epimer derivatives themselves induced increases in cell differentiation. Especially, (11S)-3,3-(ethylenedioxy) eudesmano-13-ol-6 beta-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)(2)D-3 or ATRA. The ability to enhance the differentiation potential of 1,25-(OH)(2)D-3 or ATRA by 7 may improve outcomes in the therapy of acute promyelocytic leukemia.
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