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Updated: Jul 5, 2025

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
Pentafluorosulfanyl-substituted biaryl derivatives as MATE-type transporter inhibitors targeting drug-resistant
Susumu Shinya1, Kentaro Kawai1, Naoki Kobayashi2
1Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Abstract:
Multidrug and toxin extrusion (MATE) inhibitors improve the antimicrobial susceptibility of drug-resistant bacteria by preventing the efflux of administered antibiotics. In this study, we optimized the chemical structure of a previously identified bacterial-selective MATE inhibitor 1 (EC50 > 30 µM) to improve its activity further. Compound 1 was divided into three fragments (aromatic part, linker part, and guanidine part), and each part was individually optimized. Compound 31 (EC50 = 1.8 µM), a novel pentafluorosulfanyl-containing molecule synthesized following optimized parts, showed antimicrobial activity against MATE-expressing strains at concentrations lower than conventional inhibitor 1 when co-administrated with norfloxacin. Furthermore, 31 was not cytotoxic at effective concentrations. This suggests that compound 31 can be a promising candidate for combating bacterial infections, particularly those resistant to conventional antibiotics by MATE expression.
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