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Mar. Drugs 2012, 10, 1027-1036; doi:10.3390/m OPEN ACCESS Marine Drugs ISSN 1660-3397 /journal/marinedrugs Article Woodylides A–C, New Cytotoxic Linear Polyketides from the South China Sea Sponge Plakortis simplex Hao-Bing Yu 1, Xiang-Fang Liu 2, Ying Xu 1, Jian-Hong Gan 1,3, Wei-Hua Jiao 1, Yang Shen 2,* and Hou-Wen Lin 1,* 1 Laboratory of Marine Drugs, Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; E-Mails: yuhaobing1986@126.com (H.-B.Y.); xy30490@126.com (Y.X.); jhgan@ (J.-H.G.); weihuajiao@ (W.-H.J.) 2 Department of Pharmacy, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China; E-Mail: liuxiangfang0107@126.com 3 College of Food Science Technology, Shanghai Ocean University, Shanghai 201306, China * Authors to whom correspondence should be addressed; E-Mails: shenyang@ (Y.S.); franklin67@126.com (H.-W.L.); Tel./Fax: +86-21(Y.S.); +86-21(H.-W.L.). Received: 3 February 2012; in revised form: 5 April 2012 / Accepted: 16 April 2012 / Published: 7 May 2012 Abstract: Three new polyketides, woodylides A–C (1–3), were isolated from the ethanol extract of the South China Sea sponge Plakortis simplex . The structures were elucidated by spectroscopic data (IR, 1D and 2D NMR, and HRESIMS). The absolute configurations at C-3 of 1 and 3 were determined by the modified Mosher’s method. Antifungal, cytotoxic, and PTP1B inhibitory activities of these polyketides were evaluated. Compounds 1 and 3 showed antifungal activity against