title: Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.
abstract: 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 μM, and compound 15 (IC50 = 1.4 μM) showed comparable activity to the positive control rolipram (IC50 = 0.60 μM). 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.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Zhong-Bin
authors: ZB
authors: Cheng
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Ya-Lin
authors: YL
authors: Deng
authors: East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences , Shanghai 200090, People's Republic of China.
authors: Cheng-Qi
authors: CQ
authors: Fan
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Qing-Hua
authors: QH
authors: Han
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Shu-Ling
authors: SL
authors: Lin
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Gui-Hua
authors: GH
authors: Tang
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Hai-Bin
authors: HB
authors: Luo
authors: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors: Sheng
authors: S
authors: Yin
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D002681:China; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011453:Prostaglandins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011453:Prostaglandins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram