环肽 Kahalalide F m 《人 3 Alternatives 一Total Chemica Synthesis Biotechnology/Fermentation Anti-TB Activity Cyclic Depsipeptides Jasplakinolide=Jaspamide Anti-fungal R:e Discodermins A-Dfrom Discodermia kiiensis Didemnin- 等 清美 al tria cancer,and metastatic breast caneer 1 123 Hamann, M. T.; Scheuer, P. J. J. Am. Chem. Soc. 1993, 115, 5825 环 肽 Kahalalide F 2000年在欧洲就已经投入了治疗非雄激素依赖型前列腺癌的I期临床研究,目前 正在进行治疗前列腺癌II期临床研究。F具有与其他抗肿瘤药不同的作用机制, 它选择性地改变肿瘤细胞的溶酶体膜,干扰前列腺、结直肠和肺癌细胞系的溶酶 体功能,通过非调亡机制的细胞死亡程序诱导细胞死亡,而不是阻滞细胞周期和降 解DNA,以及在动物模型中显示对肺和乳腺癌有抗肿瘤活性。 H N O N H NH N O O NH HN NH O O O O HO N H O H2N HN O NH O NH N H HN O O O O O Sea hare Elysia rufescrens Algal diet Bryopsis sp. 124 In 2005, M. Hamman & R. Hill have reported two marine bacteria Vibrio sps. as producers of this compound 125 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 126 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 127 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 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。 128 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. Didemnin-B O O NH O NH N O O O OH N H3C O O OMe NH O N N O OH O O Didemnins 的來源