Importance of the 6'-hydroxy group and its configuration for apramycin activity

Abstract

A series of apramycin derivatives was prepared and investigated for antibacterial activity and the ability to inhibit protein synthesis in cell-free translation assays. The effect of various modifications at the 6'- and N7'-positions on antiribosomal activity is discussed in terms of their influence on drug binding to specific residues in the decoding A-site. These studies contribute to the development of a structure-activity relationship for the antibacterial activity of the apramycin class of aminoglycosides and to the future design and development of more active and less toxic antibiotics.