Hopp D Craig, Rabenstein John, Rhea Joshua, Smith Chris, Romari Khadidja, Clarke Midori, Francis Linda, Irigoyen Macarena, Milanowski Dennis, Luche Michele, Carr Grant J, Mocek Ulla
AMRI, Bothell Research Center, Bothell, WA 98011, USA.
J Antibiot (Tokyo). 2008 Nov;61(11):675-9. doi: 10.1038/ja.2008.95.
Resistance to currently available antibiotics has become a widely recognized crisis in the medical community. To address this, many companies and researchers are refocusing their attention towards natural products, which have an excellent track record of producing effective antibacterial drugs. The AMRI natural product library was screened for activity against multi-drug resistant Staphylococcus aureus (MDRSA). The active samples were counter screened for cytotoxicity against the human hepatocellular carcinoma HepG2 cell line to determine an in vitro therapeutic index (in vitro TI). Those samples with a high in vitro TI were selected for fractionation and dereplication. This led to the discovery of a new anthracycline structure. This metabolite, named mutactimycin E (1), exhibited moderate activity against several gram positive organisms. Here we report the isolation, structure elucidation and biological activities of this new compound.
对当前可用抗生素产生耐药性已成为医学界广泛认可的危机。为解决这一问题，许多公司和研究人员正将注意力重新转向天然产物，天然产物在生产有效抗菌药物方面有着出色的记录。对AMRI天然产物文库进行了针对多重耐药金黄色葡萄球菌（MDRSA）活性的筛选。对活性样品进行了针对人肝癌HepG2细胞系的细胞毒性反筛选，以确定体外治疗指数（体外TI）。选择那些具有高体外TI的样品进行分离和去重复。这导致发现了一种新的蒽环类结构。这种代谢产物，命名为变活霉素E（1），对几种革兰氏阳性菌表现出中等活性。在此我们报告这种新化合物的分离、结构解析及生物活性。
