16α， 17α-环己孕酮可能代谢物的合成及其在激素依赖性乳腺癌细胞系中的抗增殖活性评价

IF 1.7 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Russian Chemical Bulletin Pub Date : 2025-09-12 DOI:10.1007/s11172-025-4737-9

M. O. Tserfas, F. B. Bogdanov, A. L. Mikhaylova, Yu. V. Kuznetsov, I. V. Zavarzin, A. M. Scherbakov, I. S. Levina

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引用次数: 0

摘要

通过还原3-酮基团并进行Mitsunobu型构型反转，合成了孕酮16α、17α-环己孕酮1可能的代谢产物，即3α-羟基-、3β-羟基-16α、17α-环己-5α-孕酮20- 1和3α-羟基-16α、17α-环己-5α-孕酮20- 1。对合成的化合物和黄体酮1对激素依赖性乳腺癌MCF-7和T47D细胞的抗增殖活性的研究表明，获得的a环双键类固醇保留了黄体酮1的抗增殖活性，IC50为22-34 μ mol L−1，而5α-还原类似物在高达50 μ mol L−1的剂量下几乎无活性。

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Synthesis of possible metabolites of 16α, 17α-cyclohexaprogesterone and evaluation of their antiproliferative activity in hormone-dependent breast cancer cell lines

Possible metabolites of progestin 16α, 17α-cyclohexaprogesterone 1, namely, 3α-hydroxy-, 3β-hydroxy-16α, 17α-cyclohexapregn-4-en-20-one, and 3α-hydroxy-16α, 17α-cyclohexa-5α-pregnan-20-one, were synthesized by reduction of the 3-keto group and subsequent Mitsunobu type inversion of configuration of the obtained alcohols. Study of the antiproliferative activity of the synthesized compounds and progestin 1 against MCF-7 and T47D cells in hormone-dependent breast cancer showed that the obtained steroids with a double bond in ring A retain the antiproliferative activity of progestin 1 with an IC₅₀ of 22–34 µmol L⁻¹, while the 5α-reduced analogs are practically inactive at doses up to 50 µmol L⁻¹.

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来源期刊

Russian Chemical Bulletin 化学-化学综合

CiteScore

2.70

自引率

47.10%

发文量

257

审稿时长

3-8 weeks

期刊介绍： Publishing nearly 500 original articles a year, by leading Scientists from Russia and throughout the world, Russian Chemical Bulletin is a prominent international journal. The coverage of the journal spans practically all areas of fundamental chemical research and is presented in five sections: General and Inorganic Chemistry; Physical Chemistry; Organic Chemistry; Organometallic Chemistry; Chemistry of Natural Compounds and Bioorganic Chemistry.