Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, 100 Dairy Rd, Pullman, WA 99164, USA.
Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA.
Mar Drugs. 2022 Mar 30;20(4):240. doi: 10.3390/md20040240.
sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti- natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against . A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of . Bioassay guided fractionation of active fractions from a deep-sea sponge, sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti- activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti- compounds and supports the importance of screening natural product libraries for new chemical scaffolds.
种是顶复门寄生虫，可导致人类和有价值的牲畜严重发病甚至死亡。目前市场上没有针对受这种寄生虫严重影响人群的有效药物。本研究是首次针对来自独特海洋化合物库的有效天然产物进行高通量筛选。佛罗里达大西洋大学港岸海洋学研究所拥有各种海洋生物的集合，其中一些已经经过中压液相色谱处理，以创建富含馏分的文库。从该文库中发现了许多活性化合物，但尚未对其进行测试。本研究使用高通量体外生长抑制测定法对库中的 3764 个馏分进行了测试，结果鉴定出 23 个强烈抑制生长的馏分。从深海海绵中对活性馏分进行生物测定导向的分级分离，得到了主要活性化合物 leiodolide A。Leiodolide A 在半最大有效浓度为 103.5 nM 时显示出特定的抗活性，对人回肠结肠直肠腺癌细胞（HCT-8）、人肝癌细胞（Hep G2）、人神经母细胞瘤细胞（SH-SY5Y）和绿猴肾细胞（Vero）的选择性指数（SI）分别为 45.1、11.9、19.6 和 14.3。Leiodolide A 的独特结构为开发新型抗化合物提供了有价值的药物支架，并支持从天然产物文库中筛选新的化学支架的重要性。
