Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia.
Org Biomol Chem. 2012 Apr 7;10(13):2656-63. doi: 10.1039/c2ob06747a. Epub 2012 Feb 24.
Fractionation of a southern Australian marine sponge, Ianthella sp., yielded sixteen metabolites including a new class of pyrrolidone, ianthellidones A-F (1-6), a new class of furanone, ianthellidones G-H (7-8), new and known lamellarins, lamellarins O1 (9), O2 (10), O (11) and Q (12), plus the known 4-hydroxybenzaldehyde (13), 4-hydroxybenzoic acid (14), 4-methoxybenzoic acid (15) and ethyl 4-hydroxybenzoate (16). Structures for all Ianthella metabolites were determined by detailed spectroscopic analysis, supported by a plausible biosynthetic relationship. The ianthellidones were non-cytotoxic towards two human colon cancer cell lines (SW620 and SW620 Ad300), as well as Gram +ve and Gram -ve bacteria, and a fungus. Ianthellidone F (6) and lamellarins O2 (10) and O (11) displayed modest BACE inhibitory properties (IC(50) > 10 μM), while lamellarin O1 (9) was more potent (IC(50) < 10 μM). Lamellarin O (11) exhibited modest cytotoxicity towards SW620 and SW620 Ad300 cell lines (IC(50) > 22 μM), was an inhibitor of the multi-drug resistance efflux pump P-glycoprotein, and displayed selective growth inhibitory activity against the Gram +ve bacterium Bacillus subtilis (ATCC 6633) (IC(50) 2.5 μM).
从澳大利亚南部海域海绵 Ianthella sp. 中分离得到 16 种代谢产物，包括新的吡咯烷酮类化合物 ianthellidones A-F（1-6）、新的呋喃酮类化合物 ianthellidones G-H（7-8）、新的和已知的 lamellarin 类化合物 lamellarin O1（9）、O2（10）、O（11）和 Q（12），以及已知的 4-羟基苯甲醛（13）、4-羟基苯甲酸（14）、4-甲氧基苯甲酸（15）和 4-羟基苯甲酸乙酯（16）。所有 Ianthella 代谢产物的结构均通过详细的光谱分析确定，并通过合理的生物合成关系得到支持。ianthellidones 对两种人结肠癌细胞系（SW620 和 SW620 Ad300）以及革兰氏阳性菌和革兰氏阴性菌和真菌均无细胞毒性。Ianthellidone F（6）和 lamellarin O2（10）和 O（11）显示出适度的 BACE 抑制活性（IC50 > 10 μM），而 lamellarin O1（9）则更有效（IC50 < 10 μM）。Lamellarin O（11）对 SW620 和 SW620 Ad300 细胞系表现出适度的细胞毒性（IC50 > 22 μM），是多药耐药外排泵 P-糖蛋白的抑制剂，并对革兰氏阳性菌枯草芽孢杆菌（ATCC 6633）表现出选择性生长抑制活性（IC50 2.5 μM）。
