从澳大利亚海洋海绵Hyrtios sp.中分离、结构测定及色氨酸生物碱的细胞毒性研究

Isolation, structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp.

作者信息

Khokhar Shahan, Feng Yunjiang, Campitelli Marc R, Ekins Merrick G, Hooper John N A, Beattie Karren D, Sadowski Martin C, Nelson Colleen C, Davis Rohan A

机构信息

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

Queensland Museum, South Brisbane, QLD 4101, Australia.

出版信息

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3329-32. doi: 10.1016/j.bmcl.2014.05.104. Epub 2014 Jun 11.

DOI:10.1016/j.bmcl.2014.05.104

PMID:24973030

Abstract

Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molecules were determined following NMR and MS data analysis. Structural ambiguities in 2 were addressed through comparison of experimental and DFT-generated theoretical NMR spectral values. Compounds 1-4 were evaluated for their cytotoxicity against a prostate cancer cell line (LNCaP) and were shown to display IC50 values ranging from 0.54 to 44.9 μM.

摘要

对澳大利亚海洋海绵Hyrtios sp.的一个样本的甲醇提取物进行质谱引导分馏，除了已知代谢产物 fascaplysin（1）和 reticulatate（4）外，还分离出两种新的色氨酸生物碱，6-氧代 fascaplysin（2）和 secofascaplysic 酸（3）。通过核磁共振（NMR）和质谱（MS）数据分析确定了所有分子的结构。通过比较实验和密度泛函理论（DFT）生成的理论核磁共振光谱值，解决了2的结构模糊性问题。评估了化合物1-4对前列腺癌细胞系（LNCaP）的细胞毒性，结果显示其半数抑制浓度（IC50）值在0.54至44.9 μM之间。