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

SUBMITTER: Lin S 

PROVIDER: S-EPMC7610524 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature