Conjugated antimicrobial agents

摘要

Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

主权项

1. A method of treating a bacterial infection in a subject, the method comprising administering to the subject an effective amount of a conjugate having the general formula I:
A-X-D-Y—B  Formula I wherein: A is a quinolone antimicrobial agent; B is an aminoglycoside antimicrobial agent; X is a first spacer moiety, covalently bound to A, or absent; Y is a second spacer moiety, covalently bound to B, or absent; D is a linking moiety having the general formula II: wherein each of the wiggled lines denote covalent bond to either A-X— or B—Y—, and R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl and alkenyl, and the infection is associated with at least one bacterial strain being treatable by at least one of said quinolone antimicrobial agent and said aminoglycoside antimicrobial agent, and has developed or being prone to develop or being capable of developing a resistance to at least one of said quinolone antimicrobial agent and said aminoglycoside antimicrobial agent.