Synthesis and Cytotoxicity Evaluation of Dehydroepiandrosterone Derivatives by Iron-Catalyzed Stereoselective Hydroamination
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- Xu Jin-Bu
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
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- Bi Jin
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
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- Wen Peng
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
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- Miao Shi-Xing
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
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- Li Xiao-Huan
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
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- Gao Feng
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University
抄録
<p>The direct modification of structurally complex natural product dehydroepiandrosterone (DHEA) through iron-catalyzed direct hydroamination of DHEA with various nitro(hetero)arenes was carried out to afford 5α-arylamino-DHEAs (1–25) in good yields (53–72%). Though as a radical reaction, it features high stereoselectivity, and only the 5α-substituted derivatives were produced. The in vitro antiproliferative activity of these synthesized compounds against the human breast cancer MCF-7 cell was evaluated, showing that most of DHEA analogues possessed the moderate cytotoxic activity. The preliminary structure–activity relationship analysis revealed that the electron-withdrawing groups installed at the para-position of arylamine ring had a great contribution to the improvement of the DHEA’s cytotoxic potency. Among them, (4-trifluoromethylaniline)-DHEA (4) displayed the most potent cytotoxicity, with an IC50 value of 19.3 µM, which was 2.3-fold more active than DHEA.</p>
収録刊行物
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- ＣＨＥＭＩＣＡＬ ＆ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＢＵＬＬＥＴＩＮ
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ＣＨＥＭＩＣＡＬ ＆ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＢＵＬＬＥＴＩＮ 71 (5), 349-353, 2023-05-01
公益社団法人 日本薬学会