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Expanding the antibacterial selectivity of polyether ionophore antibiotics through diversity-focused semisynthesis.

ABSTRACT: Polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many polyether ionophores possess potent antimicrobial activity and a few selected compounds have the ability to target aggressive cancer cells. Nevertheless, ionophore function is believed to be associated with idiosyncratic cellular toxicity and, consequently, human clinical development has not been pursued. Here, we demonstrate that structurally novel polyether ionophores can be efficiently constructed by recycling components of highly abundant polyethers to afford analogues with enhanced antibacterial selectivity compared to a panel of natural polyether ionophores. We used classic degradation reactions of the natural polyethers lasalocid and monensin and combined the resulting fragments with building blocks provided by total synthesis, including halogen-functionalized tetronic acids as cation-binding groups. Our results suggest that structural optimization of polyether ionophores is possible and that this area represents a potential opportunity for future methodological innovation.

SUBMITTER: Lin S

PROVIDER: S-EPMC7610524 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Polyether ionophore resistance in a one health perspective.

Project description:Antimicrobial resistance is a major threat to human health and must be approached from a One Health perspective. Use of antimicrobials in animal husbandry can lead to dissemination and persistence of resistance in human pathogens. Polyether ionophores (PIs) have antimicrobial activities and are among the most extensively used feed additives for major production animals. Recent discoveries of genetically encoded PI resistance mechanisms and co-localization of resistance mechanisms against PIs and antimicrobials used in human medicine on transferrable plasmids, have raised concerns that use of PIs as feed additives bear potential risks for human health. This review summarizes the current knowledge on PI resistance and discusses the potential consequences of PI-usage as feed additives in a One Health perspective.

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| S-EPMC4384835 | biostudies-other

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids.

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| S-EPMC4904257 | biostudies-literature

The polyether ionophore salinomycin targets multiple cellular pathways to block proliferative vitreoretinopathy pathology.

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Genetic screening strategy for rapid access to polyether ionophore producers and products in actinomycetes.

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| S-EPMC7442340 | biostudies-literature

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| S-EPMC7395861 | biostudies-literature

Voltammetric Ion Selectivity of Thin Ionophore-Based Polymeric Membranes: Kinetic Effect of Ion Hydrophilicity.

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