Synthesis and Evaluation of Pseudomonas aeruginosa ATP Synthase Inhibitors.
| Autor: | Ciprich JF; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Buckhalt AJE; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Carroll LL; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Chen D; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., DeFiglia SA; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., McConnell RS; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Parmar DJ; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Pistor OL; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Rao AB; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Rubin ML; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Volk GE; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Steed PR; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States., Wolfe AL; Department of Chemistry and Biochemistry, University of North Carolina Asheville, One University Heights, Asheville, North Carolina 28804, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ACS omega [ACS Omega] 2022 Aug 04; Vol. 7 (32), pp. 28434-28444. Date of Electronic Publication: 2022 Aug 04 (Print Publication: 2022). |
| DOI: | 10.1021/acsomega.2c03127 |
| Abstrakt: | New antibiotics with unique biological targets are desperately needed to combat the growing number of resistant bacterial pathogens. ATP synthase, a critical protein found in all life, has recently become a target of interest for antibiotic development due to the success of the anti-tuberculosis drug bedaquiline, and while many groups have worked on developing drugs to target bacterial ATP synthase, few have been successful at inhibiting Pseudomonas aeruginosa (PA) ATP synthase specifically. PA is one of the leading causes of resistant nosocomial infections across the world and is extremely challenging to treat due to its various antibiotic resistance mechanisms for most commonly used antibiotics. Herein, we detail the synthesis and evaluation of a series of C1/C2 quinoline analogues for their ability to inhibit PA ATP synthase and act as antibiotics against wild-type PA. From this survey, we found six compounds capable of inhibiting PA ATP synthase in vitro showing that bulky/hydrophobic C1/C2 substitutions are preferred. The strongest inhibitor showed an IC Competing Interests: The authors declare no competing financial interest. (© 2022 The Authors. Published by American Chemical Society.) |
| Databáze: | MEDLINE |
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