Author/Authors :
Chang-Hsing Liang، نويسنده , , Alex Romero، نويسنده , , David Rabuka، نويسنده , , Paulo W.M. Sgarbi، نويسنده , , Kenneth A. Marby، نويسنده , , Jonathan Duffield، نويسنده , , Sulan Yao، نويسنده , , Mayling L. Cheng، نويسنده , , Yoshi Ichikawa، نويسنده , , Pamela Sears-Rogan، نويسنده , , Changyong Hu، نويسنده , , San-Bao Hwang، نويسنده , , Youe-Kong Shue، نويسنده , , Steven J. Sucheck، نويسنده ,
Abstract :
A library of 4,5- and 4,6-linked bivalent aminoglycoside (AMG) antibiotics consisting of neamine and nebramine pharmacophores have been synthesized. We probed the effect of the linker on antibiotic activity with a series of selected synthetic analogues with varied length and substituents. A number of compounds demonstrated in vitro activity against several bacterial strains and showed activity against drug resistant strains of Pseudomonas aeruginosa. Among the compounds prepared, analogues 12a–d were novel 4,6-linked AMGs containing the nebramine pharmacophore. In addition the lead compound OPT-11 possessed an ED50 of 5 mg/kg in a Staphylococcus aureus ATCC 29213 mouse protection model.
Keywords :
ribosome , 2-Deoxystreptamine , aminoglycosides , antibiotics , RNA
