2-Phenylbenzo[b]furans: Synthesis and promoting activity on estrogen biosynthesis
2-Phenylbenzo[b]furans: Synthesis and promoting activity on estrogen biosynthesis
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2-苯基苯并[b]呋喃：合成及其对雌激素生物合成的促进活性
DOI：
10.1016/j.bmcl.2016.10.013
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发表时间：
2016-11-15
影响因子：
2.7
通讯作者：
Zhang, Guolin
中科院分区：
文献类型：
--
作者：
Pu, Wenchen;Yuan, Yun;Zhang, Guolin
雌激素生物合成对于人类许多生理过程至关重要。雌激素水平异常与多种疾病密切相关，包括乳腺癌和骨质疏松症。此前我们发现2苯基苯并[b]呋喃糖苷可以促进雌激素的生物合成。为了寻找高活性的2-苯基苯并[b]呋喃，根据相应的底物范围，通过四种策略制备了54种2-苯基苯并[b]呋喃。 HEK293A 细胞的生物学评价表明，一些化合物对雌激素生物合成表现出促进活性。 2-(4-Chloropheny1)-7-methoxy苯并[b]呋喃具有最高的活性，EC50值为14.68 mu M。此外，这些化合物不影响HEK292A细胞中芳香酶的表达，表明这些2-苯基苯并[b]呋喃可能通过直接变构调节芳香酶或通过翻译后修饰间接增强雌激素生物合成。 (C) 2016 Elsevier Ltd. 保留所有权利。
Estrogen biosynthesis is pivotal to many physiological processes of human. Aberrant estrogen level is closely related to a variety of diseases, including breast cancer and osteoporosis. Previously we found that 2phenylbenzo[b]furan glycosides could promote estrogen biosynthesis. To find high active 2-phenylbenzo [b]furans, fifty-four 2-phenylbenzo[b]furans were prepared via four strategies according to corresponding substrate scopes. Biological evaluation in HEK293A cells showed that some compounds exhibited promotive activity on estrogen biosynthesis. 2-(4-Chloropheny1)-7-methoxybenzo[b]furan possessed the highest activity with EC50 value of 14.68 mu M. Furthermore, these compounds did not affect aromatase expression in HEK292A cells, indicating that these 2-phenylbenzo[b]furans might enhance estrogen biosynthesis via directly allosteric regulation of aromatase or indirectly via posttranslational modification. (C) 2016 Elsevier Ltd. All rights reserved.