Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
J Antibiot (Tokyo). 2014 Jan;67(1):121-6. doi: 10.1038/ja.2013.115. Epub 2013 Nov 13.
A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1-5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis, Bacillus subtilis, Pseudomonas aeruginosa and Burkholderia cepacia. Compounds 2-5 showed varying degrees of activity against human cells, M. tuberculosis and B. subtilis in the low μM to mid nM range but were inactive against the other strains, while 1 lacking digitoxose was inactive. Very slight structural changes in 2-5 led to varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives.
采用了一种新颖的 lumun-lumun 采样方法来获取大量的微型软体动物，包括新物种 Lienardia totopotens。反过来，我们从 L. totopotens 中培养出一株链霉菌属菌株，该菌株含有新的和已知的螺环四烯酮聚酮化合物、lobophorin（1-5）。使用光谱法阐明了结构，并评估了化合物对人细胞的细胞毒性和对结核分枝杆菌、枯草芽孢杆菌、铜绿假单胞菌和洋葱伯克霍尔德菌的活性。化合物 2-5 在低 μM 到中 nM 范围内对人细胞、结核分枝杆菌和枯草芽孢杆菌表现出不同程度的活性，但对其他菌株没有活性，而缺乏地高辛的 1 则没有活性。2-5 中的微小结构变化导致抗菌活性：细胞毒性比值不同，为合成更具选择性的衍生物提供了可能的基础。
