Khalaf Abedawn I, Waigh Roger D, Drummond Allan J, Pringle Breffni, McGroarty Ian, Skellern Graham G, Suckling Colin J
Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, U.K.
J Med Chem. 2004 Apr 8;47(8):2133-56. doi: 10.1021/jm031089x.
Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to AT tracts of DNA has been evaluated using capillary zone electrophoresis. Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole. Moreover, these compounds have low toxicity with respect to several mammalian cell lines.
描述了48种与偏端霉素类似的杂环氨基酸三聚体，它们具有多种增强亲脂性的特征。它们含有比甲基更大的烷基或环烷基；一些在N端被乙酰胺或甲氧基苯甲酰胺封闭，在C端被二甲基氨基丙基或脂肪族杂环氨基丙基取代基封闭。已使用毛细管区带电泳评估了这些化合物主要与DNA的AT序列结合的能力。几种化合物，尤其是含有噻唑的化合物，对诸如耐甲氧西林金黄色葡萄球菌和白色念珠菌等关键生物体显示出显著的抗菌活性。此外，这些化合物对几种哺乳动物细胞系具有低毒性。
