- Structure-Activity Relationship for the Picolinamide Antibacterials that Selectively Target Clostridioides difficile
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Clostridioides difficile is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. C. difficile is difficult to eradicate due to its ability to form spores, which are not susceptible to antibiotics. To address the urgent need for treating recurrent C. difficile infection, antibiotics that selectively target C. difficile over common gut microbiota are needed. We herein describe the class of picolinamide antibacterials which show potent and selective activity against C. difficile. The structure-activity relationship of 108 analogues of isonicotinamide 4, a compound that is equally active against methicillin-resistant Staphylococcus aureus and C. difficile, was investigated. Introduction of the picolinamide core as exemplified by analogue 87 resulted in exquisite potency and selectivity against C. difficile. The ability of the picolinamide class to selectively target C. difficile and to prevent gut dysbiosis holds promise for the treatment of recurrent C. difficile infection.
- Speri, Enrico,Qian, Yuanyuan,Janardhanan, Jeshina,Masitas, Cesar,Lastochkin, Elena,De Benedetti, Stefania,Wang, Man,Schroeder, Valerie A.,Wolter, William R.,Oliver, Allen G.,Fisher, Jed F.,Mobashery, Shahriar,Chang, Mayland
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supporting information
p. 991 - 995
(2021/05/27)
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- Structural tuning of ancillary chelate in tri-carboxyterpyridine Ru(ii) sensitizers for dye sensitized solar cells
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Three distinct classes of ancillary chelates, namely: 2-(3- trifluoromethylpyrazol-5-yl)-6-(3-trifluoromethylphenyl)pyridine (L3, H 2pzppy), 4-(3-trifluoromethylpyrazol-5-yl)-2-(3-trifluoromethyl) phenylpyrimidine (L5, H2pzppm) and 4-(6-(3-trifluoromethylpyrazol-5- yl)pyridin-2-yl)-2-trifluoromethylpyrimidine (L6, H2pzpypm), which showed an identical skeletal topology, but with the more electronegative nitrogen atom replacing the isoelectronic methine group at the selected skeletal position, were obtained to investigate the photophysical and electrochemical properties and hence the associated Ru(ii) sensitizers based DSCs. To increase the optical absorptivity we also strategically added thiophene (thienyl) or 3,4-ethylenedioxythiophene (EDOT) appendages to L6, for boosting the short-circuit photocurrent (JSC) and the overall efficiency (η) of the fabricated DSC devices. Under AM 1.5G illumination, the best sensitizer showed performance data of JSC = 18.11 mA cm-2, V OC = 0.66 V, FF = 0.729 and η = 8.72%, and a good cell stability at 60 °C for 1000 hours, being only decreased by ~5% in the η value.
- Chou, Chun-Cheng,Chen, Pei-Hua,Hu, Fa-Chun,Chi, Yun,Ho, Shu-Te,Kai, Ji-Jung,Liu, Shih-Hung,Chou, Pi-Tai
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p. 5418 - 5426
(2014/04/03)
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