| Autor: |
Zachary W. Boyer, Hannah Kessler, Hannah Brosman, Kirsten J. Ruud, Alan F. Falkowski, Constance Viollet, Christina R. Bourne, Matthew C. O’Reilly |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
ACS Omega. 7:37907-37916 |
| ISSN: |
2470-1343 |
| DOI: |
10.1021/acsomega.2c05071 |
| Popis: |
Antibiotic resistance among bacteria puts immense strain on public health. The discovery of new antibiotics that work through unique mechanisms is one important pillar toward combating this threat of resistance. A functionalized amino dihydropyrimidine was reported to exhibit antibacterial activity via the inhibition of dihydrofolate reductase, an underexploited antibacterial target. Despite this promise, little is known about its structure-activity relationships (SAR) and mechanism of activity. Toward this goal, the aza-Biginelli reaction was optimized to allow for the preparation of focused libraries of functionalized amino dihydropyridines, which in some cases required the use of variable temperature NMR analysis for the conclusive assignment of compound identity and purity. Antibacterial activity was examined using microdilution assays, and compound interactions with dihydrofolate reductase were assessed using antimicrobial synergy studies alongside |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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