CSIC, Department of Bioorganic Chemistry, c/Juan de la Cierva, 3, 28006-Madrid, Spain.
Org Biomol Chem. 2016 Jan 14;14(2):516-525. doi: 10.1039/c5ob01599e.
Aminoglycosides are highly potent, wide-spectrum bactericidals. N-1 modification of aminoglycosides has thus far been the best approach to regain bactericidal efficiency of this class of antibiotics against resistant bacterial strains. In the present study we have evaluated the effect that both, the number of modifications and their distribution on the aminoglycoside amino groups (N-1, N-3, N-6' and N-3''), have on the antibiotic activity. The modification of N-3'' in the antibiotic kanamycin A is the key towards the design of new aminoglycoside antibiotics. This derivative maintains the antibiotic activity against aminoglycoside acetyl-transferase- and nucleotidyl-transferase-expressing strains, which are two of the most prevalent modifying enzymes found in aminoglycoside resistant bacteria.
氨基糖苷类抗生素具有高效、广谱的杀菌作用。因此，迄今为止，对氨基糖苷类抗生素进行 N-1 修饰是恢复该类抗生素对耐药菌株杀菌效率的最佳方法。在本研究中，我们评估了修饰的数量及其在氨基糖苷类抗生素氨基上的分布（N-1、N-3、N-6'和 N-3''）对抗生素活性的影响。抗生素卡那霉素 A 中 N-3''的修饰是设计新型氨基糖苷类抗生素的关键。该衍生物保持了对抗生素乙酰转移酶和核苷酸转移酶表达菌株的抗生素活性，这两种酶是氨基糖苷类耐药菌中最常见的两种修饰酶。
