Wright Amy E, Roberts Jill C, Guzmán Esther A, Pitts Tara P, Pomponi Shirley A, Reed John K
Harbor Branch Oceanographic Institute, Florida Atlantic University , Fort Pierce, Florida 34946, United States.
J Nat Prod. 2017 Mar 24;80(3):735-739. doi: 10.1021/acs.jnatprod.6b01140. Epub 2017 Jan 30.
Two new analogues of the potent antitumor compound leiodermatolide, which we call leiodermatolides B and C, have been isolated from specimens of a deep-water sponge of the genus Leiodermatium collected off Florida. The compounds were purified using standard chromatographic methods, and the structures defined through interpretation of the HRMS and 1D and 2D NMR data. Leiodermatolide B (2) lacks the C-21 hydroxy group found in leiodermatolide and has equal potency as the parent compound, providing a simpler analogue for possible clinical development. It inhibits the proliferation of the AsPC-1 human pancreatic adenocarcinoma cell line with an IC of 43 nM. Leiodermatolide C (3) has a modified macrolide ring and is over 85-fold less potent with an IC of 3.7 μM against the same cell line. These compounds add to the knowledge of the pharmacophore of this class of potent antitumor agents.
从佛罗里达沿海采集的Leiodermatium属深水海绵标本中分离出了两种强效抗肿瘤化合物leiodermolide的新类似物，我们将其称为leiodermolides B和C。这些化合物采用标准色谱方法进行纯化，并通过对高分辨质谱（HRMS）以及一维和二维核磁共振（NMR）数据的解析确定其结构。Leiodermatolide B（2）缺少leiodermolide中存在的C-21羟基，并且与母体化合物具有同等效力，为可能的临床开发提供了一种更简单的类似物。它对AsPC-1人胰腺腺癌细胞系增殖的抑制IC50为43 nM。Leiodermatolide C（3）具有一个经过修饰的大环内酯环，对同一细胞系的效力低85倍以上，IC50为3.7 μM。这些化合物增加了我们对这类强效抗肿瘤药物药效基团的认识。
