Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi

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• 作者：Zhong-Bin Cheng ; Ya-Lin Deng ; Cheng-Qi Fan ; Qing-Hua Han ; Shu-Ling Lin ; Gui-Hua Tang ; Hai-Bin Luo ; Sheng Yin
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：August 22, 2014
• 年：2014
• 卷：77
• 期：8
• 页码：1928-1936
• 全文大小：365K
• ISSN：1520-6025

文摘

Ten new prostaglandin derivatives (PGs), sarcoehrendins A鈥揓 (1鈥?b>10), together with five known analogues (11鈥?b>15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4鈥?b>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鈥?b>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鈥?b>15 exhibited inhibition with IC₅₀ values less than 10 渭M, and compound 15 (IC₅₀ = 1.4 渭M) showed comparable activity to the positive control rolipram (IC₅₀ = 0.60 渭M). The active natural PGs (2, 10, and 13鈥?b>15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure鈥揳ctivity relationship is also proposed.