| Autor: |
Michael J, Zeiler, Gina M, Connors, Greg M, Durling, Allen G, Oliver, Lewis, Marquez, Roberta J, Melander, Cassandra L, Quave, Christian, Melander |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Angew Chem Int Ed Engl |
| ISSN: |
1521-3773 |
| Popis: |
Over the past decades, antibiotic resistance has grown to a point where orthogonal approaches to combating infections caused by resistant bacteria are needed. One such approach is the development of non-microbicidal small molecules that potentiate the activity of conventional antibiotics, termed adjuvants. The diterpene natural product 12(S),16ε-Dihydroxycleroda-3,13-dien-15,16-olide, which we refer to as (−)-LZ-2112, is known to synergize with oxacillin against methicillin-resistant Staphylococcus aureus (MRSA). To explore this activity, (−)-LZ-2112 was synthesized and the structure confirmed through X-ray analysis. Preliminary structure-activity relationship studies following the synthesis of several analogues identified key structural elements responsible for activity and indicate that scaffold simplification is possible. A preliminary mode of action study suggests mecA plays a role in the adjuvant activity of (−)-LZ-2112. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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