Issue 7, 2017

Bifunctional antimicrobial conjugates and hybrid antimicrobials

Abstract

Covering: up to the end of 2016

Novel antimicrobial drugs are continuously needed to counteract bacterial resistance development. An innovative molecular design strategy for novel antibiotic drugs is based on the hybridization of an antibiotic with a second functional entity. Such conjugates can be grouped into two major categories. In the first category (antimicrobial hybrids), both functional elements of the hybrid exert antimicrobial activity. Due to the dual targeting, resistance development can be significantly impaired, the pharmacokinetic properties can be superior compared to combination therapies with the single antibiotics, and the antibacterial potency is often enhanced in a synergistic manner. In the second category (antimicrobial conjugates), one functional moiety controls the accumulation of the other part of the conjugate, e.g. by mediating an active transport into the bacterial cell or blocking the efflux. This approach is mostly applied to translocate compounds across the cell envelope of Gram-negative bacteria through membrane-embedded transporters (e.g. siderophore transporters) that provide nutrition and signalling compounds to the cell. Such ‘Trojan Horse’ approaches can expand the antibacterial activity of compounds against Gram-negative pathogens, or offer new options for natural products that could not be developed as standalone antibiotics, e.g. due to their toxicity.

Graphical abstract: Bifunctional antimicrobial conjugates and hybrid antimicrobials

Article information

Article type
Review Article
Submitted
24 Janv. 2017
First published
22 Maijs 2017

Nat. Prod. Rep., 2017,34, 832-885

Bifunctional antimicrobial conjugates and hybrid antimicrobials

P. Klahn and M. Brönstrup, Nat. Prod. Rep., 2017, 34, 832 DOI: 10.1039/C7NP00006E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements