biostudies-literatureUnknown26(24)Watson DJWith drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K+, NH4+ and Na+. Combination studies using the fMolecules (Basel, Switzerland)7494https://www.ebi.ac.uk/biostudies/studies/S-EPMC8708982biostudies-literatureDiscovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin.PMC8708982Dziwornu GABarnett CBAcquah KSWiesner LWatson DJMeyers PRfalseDiscovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin.With drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K+, NH4+ and Na+. Combination studies using the f2021-01-01T00:00:00Z2021 Dec2025-04-19T00:52:49.431Z2022-02-11T14:29:54.479ZS-EPMC87089823494657710.3390/molecules26247494