Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
J Nat Prod. 2011 Aug 26;74(8):1677-85. doi: 10.1021/np200270d. Epub 2011 Aug 1.
Two new grassypeptolides and a lyngbyastatin analogue, together with the known dolastatin 12, have been isolated from field collections and laboratory cultures of the marine cyanobacterium Leptolyngbya sp. collected from the SS Thistlegorm shipwreck in the Red Sea. The overall stereostructures of grassypeptolides D (1) and E (2) and Ibu-epidemethoxylyngbyastatin 3 (3) were determined by a combination of 1D and 2D NMR experiments, MS analysis, Marfey's methodology, and HPLC-MS. Compounds 1 and 2 contain 2-methyl-3-aminobutyric acid and 2-aminobutyric acid, while biosynthetically distinct 3 contains 3-amino-2-methylhexanoic acid and the β-keto amino acid 4-amino-2,2-dimethyl-3-oxopentanoic acid (Ibu). Grassypeptolides D (1) and E (2) showed significant cytotoxicity to HeLa (IC₅₀ = 335 and 192 nM, respectively) and mouse neuro-2a blastoma cells (IC₅₀ = 599 and 407 nM, respectively), in contrast to Ibu-epidemethoxylyngbyastatin 3 (neuro-2a cells, IC₅₀ > 10 μM) and dolastatin 12 (neuro-2a cells, IC₅₀ > 1 μM).
从红海 SS Thistlegorm 号沉船中采集的海洋蓝藻 Leptolyngbya sp. 的野外采集和实验室培养物中分离出两种新的 grassypeptolide 和一种 lyngbyastatin 类似物，以及已知的 dolastatin 12。通过 1D 和 2D NMR 实验、MS 分析、Marfey 方法和 HPLC-MS 的组合，确定了 grassypeptolide D（1）和 E（2）以及 Ibu-epidemethoxylyngbyastatin 3（3）的总体立体结构。化合物 1 和 2 含有 2-甲基-3-氨基丁酸和 2-氨基丁酸，而生物合成上不同的 3 含有 3-氨基-2-甲基己酸和β-酮氨基酸 4-氨基-2,2-二甲基-3-氧代戊酸（Ibu）。Grassypeptolide D（1）和 E（2）对 HeLa（IC₅₀=335 和 192 nM，分别）和小鼠神经-2a 成神经细胞瘤细胞（IC₅₀=599 和 407 nM，分别）表现出显著的细胞毒性，而 Ibu-epidemethoxylyngbyastatin 3（神经-2a 细胞，IC₅₀>10 μM）和 dolastatin 12（神经-2a 细胞，IC₅₀>1 μM）则没有。
