| Autor: |
Radleigh G. Santos, Renee Fleeman, Adel Nefzi, Travis LaVoi, José L. Medina-Franco, Lindsey N. Shaw, Gregory S. Welmaker, Marc A. Giulianotti, Richard A. Houghten, Angela Morales |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
J Med Chem |
| ISSN: |
1520-4804 |
| Popis: |
Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10,000 and 750,000 structural analogs for a total of >6 million compounds. From this we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
