Harrigan G G, Yoshida W Y, Moore R E, Nagle D G, Park P U, Biggs J, Paul V J, Mooberry S L, Corbett T H, Valeriote F A
Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822.
J Nat Prod. 1998 Oct;61(10):1221-5. doi: 10.1021/np9801211.
Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.
林格比他汀1（1a）是多拉司他汀12（2a）和多拉司他汀11（4）的一种新型细胞毒性类似物，它是从关岛附近采集的一种巨大鞘丝藻/钙生裂须藻组合体和一株巨大鞘丝藻菌株的提取物中，与其C-15差向异构体（1b）作为不可分离的混合物分离得到的。在巨大鞘丝藻/钙生裂须藻组合体中，多拉司他汀12（2a）也与其C-15差向异构体（2b）作为不可分离的混合物被发现。每个混合物中的至少一种化合物在溶液中似乎以缓慢相互转化的构象异构体混合物形式存在，导致1H NMR谱中的信号变宽。因此，结构解析主要依赖于质谱和化学降解研究。当用1ab和2ab针对结肠腺癌#38或乳腺腺癌#16/C进行测试时，两者均显示出毒性，但仅具有微弱或无抗肿瘤活性。1ab和2ab均被证明是细胞微丝网络的有效破坏剂。
