nTZDpa (non-thiazolidinedione PPARγ partial agonist) derivatives retain antimicrobial activity without improving renal toxicity
| Autor: | Madeline M, Dekarske, Lewis Oscar, Felix, Carlos Monteagudo, Ortiz, Erika E, Csatary, Elefterios, Mylonakis, William M, Wuest |
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| Rok vydání: | 2022 |
| Předmět: |
Staphylococcus aureus
Organic Chemistry Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Staphylococcal Infections Biochemistry Article Anti-Bacterial Agents PPAR gamma Structure-Activity Relationship Anti-Infective Agents Drug Discovery Humans Molecular Medicine Molecular Biology |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 0960-894X |
| Popis: | nTZDpa kills both growing and persister Staphylococcus aureus. However, due to toxicity liabilities, our lab conducted two structure–activity relationship (SAR) studies focusing on the core scaffold and obtained a new lead compound that was more potent and less hemolytic. Despite these favorable changes, the new lead displayed toxicity to renal cells. In this SAR study, we sought to improve this renal toxicity by derivatization via changes to sp(3) character, the acid moiety, and halogenation of the aryl rings. Presented herein are our efforts that produced potent compounds albeit with no improvement to renal cell toxicity. |
| Databáze: | OpenAIRE |
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