Barker Lucia P, Lien Benjamin A, Brun Olivier S, Schaak Damen D, McDonough Kathleen A, Chang Leng Chee
University of Minnesota Medical School, Department of Anatomy Microbiology and Pathology, Duluth, MN, USA.
Planta Med. 2007 Jun;73(6):559-63. doi: 10.1055/s-2007-981522. Epub 2007 May 30.
A novel screening method for antimycobacterial agents using Mycobacterium marinum was developed. M. marinum was selected as a model organism because it has a close phylogenetic relationship to M. tuberculosis, a relatively rapid doubling time, similar drug susceptibilities to M. tuberculosis, and less stringent safety requirements. More than 1000 crude marine and plant extracts were screened against M. marinum in a Zone of Inhibition (ZOI) assay, and twenty-one target extracts were identified. The crude organic extract of the marine sponge, Haliclona sp.10, was chosen for further investigation as it yielded a ZOI of 20 mm at a concentration of 80 microg/disk. Following bioassay-guided fractionation, (-)-papuamine was isolated, and yielded a 15 mm ZOI at a concentration of 25 microg/disk. In standard assays using M. marinum, (-)-papuamine exhibited both an MIC and an MBC95 of 6.25 microg/mL. This is the first report of antimycobacterial activity for (-)-papuamine. In addition, when (-)-papuamine and other natural product extracts were tested for activity against both M. marinum and M. tuberculosis, activity was comparable between the two species. These data indicate that (-)-papuamine is a promising lead for the development of new antimycobacterial agents and that M. marinum is a useful surrogate for the screening of antimycobacterial compounds.
开发了一种使用海分枝杆菌筛选抗分枝杆菌药物的新方法。选择海分枝杆菌作为模式生物，因为它与结核分枝杆菌具有密切的系统发育关系，倍增时间相对较快，对结核分枝杆菌的药物敏感性相似，并且安全要求不太严格。在抑菌圈（ZOI）试验中，针对海分枝杆菌筛选了1000多种海洋和植物粗提物，鉴定出21种目标提取物。海洋海绵Haliclona sp.10的粗有机提取物被选作进一步研究对象，因为在浓度为80微克/圆盘时其产生的抑菌圈为20毫米。经过生物测定指导的分级分离，分离出了（-）-帕普胺，在浓度为25微克/圆盘时产生了15毫米的抑菌圈。在使用海分枝杆菌的标准试验中，（-）-帕普胺的最低抑菌浓度（MIC）和95%最低杀菌浓度（MBC95）均为6.25微克/毫升。这是关于（-）-帕普胺抗分枝杆菌活性的首次报道。此外，当测试（-）-帕普胺和其他天然产物提取物对海分枝杆菌和结核分枝杆菌的活性时，两种菌株之间的活性相当。这些数据表明，（-）-帕普胺是开发新型抗分枝杆菌药物的有前景的先导物，并且海分枝杆菌是筛选抗分枝杆菌化合物的有用替代物。
