河北医科大学药学院 Anti-TB Activity Cyclic Depsipeptides 】 2:y 人 Microcystin-LR微囊藻毒素 Jasplakinolide=Jaspamide Anti-fungal HO Discodermins A-D from Discodermia kiiensis Didemnin-B 风情分清得为人运康果精 便逢刺的落性， 天然药化教研室史清文教授 河北医科大学药学院 天然药化教研室史清文教授 7 Anti-TB Activity Cyclic Depsipeptides K. A. El Sayed et al. Tetrahedron 2000, 56: 949–953 Massetolide-A and Viscosin are the first example of marine derived peptide having antimicrobacterial tuberculosis activity. Massetolide-A Viscosin Isolated from algae with anti-TB and progressed in clinic trial. Gerard, J et al.. J. Nat. Prod. 1997, 60, 223. Burke, T. Ret al. Tetrahedron Lett. 1989, 30, 519. HN HN NH OH O O NH O O O NH H N O N H O O H N O OH HN HO O O O R 1 R = Me 2 R = H Microcystin-LR 1996年在巴西造成100多名急性肝功能障碍，7个月内至少50人死于 藻毒素产生的急性效应，引起举世瞩目的关注。 微囊藻毒素 Jasplakinolide = Jaspamide Anti-fungal NH N NH O O O O O NH Br HO Fusetani N. Bioctive Sponge Peptides. Chem. Rev. 1993, 93:11793-1806. 伏谷 伸宏 Discodermins A-D from Discodermia kiiensis. Matsunaga, S.; Fusetani, N.; Konosu, S. Tetrahedron Lett. 1984, 25, 5165. Matsunaga, S.; Fusetani, N.; Konosu, S. Tetrahedron Lett. 1985, 26, 855. N NH N NH HN N H H N N H H N N O O R1 R2 O O NH O O HN O H HN O NH H2N NH O SO3 O HN O O NH2 HN H N O N O OH O O O CONH2 Discodermin A R1=R2=Me Discodermin B R1=H, R2=Me Discodermin C R1=Me, R2=H Discodermin D R1=R2=H 从海绵中分离得到的活性肽类化合物，discodermins是磷酸酯 酶A2抑制剂(IC50为3.5-7.010–7 M)。A还具有抗炎和抑制肿瘤 促进剂的活性。 Didemnins A-C were isolated from Trididemnum solidum, a Caribbean tunicate (加拉比海鞘). Didemnin-B has completed phase II human clinical trials against advanced adenocarcinoma of the kidney, advanced epithelial ovarian cancer, and metastatic breast cancer. 但因心脏 和神经毒性而被放弃。 Didemnin-B Trididemnum solidum 膜海鞘素B O O NH O NH N O O O OH N CH3 O O OMe NH O N N O OH O O