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Synthesis of 4-substituted Androst-4-ene and 6-substituted Androstane Derivatives, Aromatase Inhibitory Activity and Cytotoxicity
Yakhak Hoeji 2020;64(6):465-474
Published online December 31, 2020
© 2020 The Pharmaceutical Society of Korea.

Min Woo Kim* and Eunsook Ma**,#

*Ministry of Food and Drug Safety
**College of Pharmacy, Daegu Catholic University
Correspondence to: Eunsook Ma, College of Pharmacy, Daegu Catholic University, 13-13 Hayang-ro, Gyeongsan-si, 38430, Korea
Tel: +82-53-830-3621, Fax: +82-53-850-3602
Received November 21, 2020; Revised December 9, 2020; Accepted December 15, 2020.
The development of potent aromatase inhibitors is an important therapeutic strategy for the treatment of breast cancer in postmenopausal women. Synthesized compounds that act as both an aromatase inhibitor and an anti–breast cancer agent are especially effective. In this study, nine 4-substituted androst-4-ene derivatives were synthesized from dehydroepiandrosterone via Jones oxidation, epoxidation, epoxy ring-opening, and dehydration reactions. Five 6-substituted androstane derivatives were synthesized from dehydroepiandrosterone via epoxidation and epoxy ring-opening reactions. Screening assays were used to assess the synthesized compounds for potential inhibitory effects against aromatase; results showed that compared to other compounds, 2 µM of 4-azido-17,17-ethylenedioxyandrost-4-en-3-one (10) had the greatest inhibitory effect (94.70%) against aromatase activity in human placental microsomes. A 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) colorimetric assay was used to analyze the activity of 13 compounds against two human breast cancer cell lines (ER+ T47D and ER MDA-MB-231). Compounds 10 and 12 showed strong cytotoxic activity against MDA-MB-231 (IC50: 25.6 and 32.7 µM, respectively).
Keywords : breast cancer, aromatase inhibitor, cytotoxicity, androstene, androstane

December 2020, 64 (6)
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