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KMID : 0370220200640040465
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Yakhak Hoeji
2020 Volume.64 No. 4 p.465 ~ p.474
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Synthesis of 4-substituted Androst-4-ene and 6-substituted Androstane Derivatives, Aromatase Inhibitory Activity and Cytotoxicity
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Kim Min-Woo
Ma Eun-Sook
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Abstract
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The development of potent aromatase inhibitors is an important therapeutic strategy for the treatment of breastcancer in postmenopausal women. Synthesized compounds that act as both an aromatase inhibitor and an anti?breastcancer agent are especially effective. In this study, nine 4-substituted androst-4-ene derivatives were synthesized fromdehydroepiandrosterone via Jones oxidation, epoxidation, epoxy ring-opening, and dehydration reactions. Five 6-substitutedandrostane 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; resultsshowed that compared to other compounds, 2 μM of 4-azido-17,17-ethylenedioxyandrost-4-en-3-one (10) had the greatestinhibitory 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 twohuman breast cancer cell lines (ER+ T47D and ER MDA-MB-231). Compounds 10 and 12 showed strong cytotoxicactivity against MDA-MB-231 (IC50: 25.6 and 32.7 μM, respectively).
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KEYWORD
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breast cancer, aromatase inhibitor, cytotoxicity, androstene, androstane
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