Activity-guided isolation of steroidal alkaloid antiestrogen-binding site inhibitors from Pachysandra procumbens
Activity-guided isolation of steroidal alkaloid antiestrogen-binding site inhibitors from Pachysandra procumbens
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DOI：
10.1021/np980162x
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发表时间：
1998-10-01
影响因子：
5.1
通讯作者：
Kinghorn, AD
中科院分区：
文献类型：
--
作者：
Chang, LC;Bhat, KPL;Kinghorn, AD
四种新型甾体生物碱，(+)-(20S)-20-(二甲氨基)-3-(3'α-异丙基)-lactam-5 alpha-pregn-2-en-4-one (1)、(+)-(20S)-20-(二甲氨基)-16 α-羟基-3-(3'α-异丙基)-lactam-5 alpha-preg-2-en-4-one (2)、(+)-(20S)-3-(苯甲酰氨基)-20-(二甲氨基)-5 α-pregn-2-en-4 β-乙酸酯(3)和(+)-(20S)-2 α-羟基-20-(二甲氨基)-3 β-邻苯二甲酰亚胺基-5 α-pregnan-4 β-乙酸酯(4)，以及五种已知化合物，(-)-pachyaximine A (5)，使用基于抑制 H-3-他莫昔芬在抗雌激素结合位点 (AEBS) 结合的生物测定指导分级分离，从厚生草中分离出 (+)-螺粗胺 (6)、(+)-腋臭胺 A (7)、(+)-表粗胺 D (8) 和 (+)-厚胺 B (9)。化合物1-7和9表现出作为AEBS抑制剂的显着活性，并且发现化合物3、5和9在培养的Ishikawa细胞中显着增强由他莫昔芬介导的抗雌激素作用。通过光谱数据解释进行了化合物1-4的结构解析。
Four novel steroidal alkaloids, (+)-(20S)-20-(dimethylamino)-3-(3'alpha-isopropopyl)-lactam-5 alpha-pregn-2-en-4-one (1), (+)-(20S)-20-(dimethylamino)-16 alpha-hydroxy-3-(3'alpha-isopropyl)-lactam-5 alpha-preg-2-en-4-one (2), (+)-(20S)-3-(benzoylamino)-20-(dimethylamino)-5 alpha-pregn-2-en-4 beta-yl acetate (3), and (+)-(20S)-2 alpha-hydroxy-20-(dimethylamino)-3 beta-phthalimido-5 alpha-pregnan-4 beta-yl acetate (4), as well as five known compounds, (-)-pachyaximine A (5), (+)-spiropachysine (6), (+)-axillaridine A (7), (+)-epipachysamine D (8), and (+)-pachysamine B (9), were isolated from Pachysandra procumbens, using a bioassay-guided fractionation based on inhibition of H-3-tamoxifen binding at the antiestrogen binding site (AEBS). Compounds 1-7 and 9 demonstrated significant activity as AEBS-inhibitory agents, and compounds 3, 5 and 9 were found to potentiate significantly the antiestrogenic effect mediated by tamoxifen in cultured Ishikawa cells. The structure elucidation of compounds 1-4 was carried out by spectral data interpretation.