Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi
Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi
复制标题
前列腺素衍生物：来自软珊瑚肉菌 ehrenbergi 的非芳香族磷酸二酯酶 4 抑制剂
DOI：
10.1021/np500394d
复制
发表时间：
2014-08-01
影响因子：
5.1
通讯作者：
Yin, Sheng
中科院分区：
文献类型：
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作者：
Cheng, Zhong-Bin;Deng, Ya-Lin;Yin, Sheng
从软珊瑚Sarcophyton ehrenbergi中分离得到10个新的前列腺素衍生物（PGs），即Sarcoehrendins A-J（1-10）和5个已知的类似物（11-15）。化合物4-8代表具有18-酮基的PG的第一个实例。根据光谱分析和化学证据确定了化合物的结构，包括绝对构型。筛选了所有分离物和6种合成类似物（3a、3b、4a和11 a-11 c）对磷酸二酯酶-4（PDE 4）的抑制活性，PDE 4是治疗哮喘和慢性阻塞性肺病的药物靶标。化合物2、10、11 a、11 b和13-15显示出抑制作用，IC 50值小于10 μ M，化合物15（IC 50 = 1.4 μ M）显示出与阳性对照咯利普兰（IC 50 = 0.60 μ M）相当的活性。活性天然PG（2，10，和13-15）代表的第一个例子没有芳香族部分的PDE 4抑制剂，并提出了初步的结构-活性关系。
Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 mu M, and compound 15 (IC50 = 1.4 mu M) showed comparable activity to the positive control rolipram (IC50 = 0.60 mu M). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.