Issac Michal, Aknin Maurice, Gauvin-Bialecki Anne, De Voogd Nicole, Ledoux Alisson, Frederich Michel, Kashman Yoel, Carmeli Shmuel
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Ramat Aviv, Tel-Aviv 69978, Israel.
Laboratoire de Chimie des Substances Naturelles et des Aliments, Faculté des Sciences et Technologies, Université de La Réunion , 15 Avenue René Cassin, CS 92 003, 97 744, Saint-Denis, Cedex 9, France.
J Nat Prod. 2017 Apr 28;80(4):1110-1116. doi: 10.1021/acs.jnatprod.7b00028. Epub 2017 Feb 16.
The extract of a sample of the sponge Theonella aff. swinhoei collected in Madagascar exhibited promising in vitro antiplasmodial activity. The antiplasmodial activity was ascribed in part to the known metabolite swinholide A. Further investigation of the extract afforded three unusual cyclic peptides, cyclotheonellazoles A-C (1-3), which contain six nonproteinogenic amino acids out of the eight acid units that compose these natural products. Among these acids the most novel were 4-propenoyl-2-tyrosylthiazole and 3-amino-4-methyl-2-oxohexanoic acid. The structure of the compounds was elucidated by interpretation of the 1D and 2D NMR data, HRESIMS, and advanced Merfay's techniques. The new compounds were found to be nanomolar inhibitors of chymotrypsin and sub-nanomolar inhibitors of elastase, but did not present antiplasmodial activity.
在马达加斯加采集的拟斯氏海绵（Theonella aff. swinhoei）样本提取物显示出有前景的体外抗疟活性。该抗疟活性部分归因于已知代谢产物斯氏大环内酯A（swinholide A）。对该提取物的进一步研究得到了三种不同寻常的环肽，即环西奥奈拉唑A - C（1 - 3），在构成这些天然产物的八个酸单元中有六个是非蛋白氨基酸。在这些酸中，最新颖的是4 - 丙烯酰基 - 2 - 酪氨酰噻唑和3 - 氨基 - 4 - 甲基 - 2 - 氧代己酸。通过对一维和二维核磁共振数据、高分辨电喷雾电离质谱（HRESIMS）以及先进的Merfay技术的解释阐明了这些化合物的结构。发现这些新化合物是胰凝乳蛋白酶的纳摩尔抑制剂和弹性蛋白酶的亚纳摩尔抑制剂，但没有抗疟活性。
