Antibiotic Potency against E. coli Is Enhanced by Channel-Forming Alkyl Lariat Ethers.
Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to significantly enhance the potency of rifampicin and tetracycline, but not erythromycin and kanamycin, against the non-pathogenic DH5α and K-12 strains of Escherichia coli when administered at levels below their minimum inhibitory concentrations (MICs). The enhancements in antibiotic potency observed for the lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli, the antibiotic, and the lengths of the alkyl chains attached at the macroring nitrogen atoms. The dialkyl lariat ethers, previously thought to only be cation carriers, formed well-behaved, ion-conducting pores in soybean asolectin membranes, as judged by planar bilayer conductance measurements. The ability of lariat ethers to form stable pores, which appeared to be aggregated, depended in part on alkyl chain length and in part on the composition of the bilayer membrane in which they were studied.
Department of Chemistry and Biochemistry, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Upaya Pharmaceuticals, LLC, 4633 World Parkway, Berkeley, MO, 63134, USA.
Saeedeh
http://orcid.org/0000-0002-8917-524X
S
Negin
Department of Biology, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Upaya Pharmaceuticals, LLC, 4633 World Parkway, Berkeley, MO, 63134, USA.
Mohit B
MB
Patel
Upaya Pharmaceuticals, LLC, 4633 World Parkway, Berkeley, MO, 63134, USA.
Michael R
http://orcid.org/0000-0002-2341-9117
MR
Gokel
Center for Nanoscience, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Department of Chemistry and Biochemistry, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.
Joseph W
http://orcid.org/0000-0003-3348-0242
JW
Meisel
Center for Nanoscience, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Department of Chemistry and Biochemistry, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Department of Biology, University of Missouri, 1 University Blvd., St. Louis, MO, 63121, USA.|Upaya Pharmaceuticals, LLC, 4633 World Parkway, Berkeley, MO, 63134, USA.
George W
http://orcid.org/0000-0003-3994-6795
GW
Gokel
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047248:Crown Compounds / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D004987:Ethers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology; D013752:Tetracycline / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047248:Crown Compounds; D004987:Ethers; D008051:Lipid Bilayers; D013752:Tetracycline; D012293:Rifampin
antibiotics; channel function; lariat ethers; planar bilayer conductance; pore formation