Structure-activity relationships of pyrazole-4-carbodithioates as antibacterials against methicillin–resistant Staphylococcus aureus
| Autor: | Michael J. Kelso, Tatiana Johnston, Nicholas E. Dixon, Hiwa Majed, Eleftherios Mylonakis, Slobodan Jergic, Enrico Monachino, Celine Kelso |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Staphylococcus aureus medicine.drug_class 030106 microbiology Clinical Biochemistry Antibiotics Pharmaceutical Science Microbial Sensitivity Tests Pyrazole medicine.disease_cause 01 natural sciences Biochemistry Article Microbiology Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Thiocarbamates Residential care Drug Discovery medicine Molecular Biology Bacteriostatic agent 010405 organic chemistry Chemistry Organic Chemistry Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents 0104 chemical sciences 3. Good health Molecular targets Pyrazoles Molecular Medicine Antibacterial action medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 28:3526-3528 |
| ISSN: | 0960-894X |
| Popis: | Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious hospital-acquired infections and is responsible for significant morbidity and mortality in residential care facilities. New agents against MRSA are needed to combat rising resistance to current antibiotics. We recently reported 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) as a new bacteriostatic agent against MRSA that appears to act via a novel mechanism. Here, twenty nine analogs of HMPC were synthesized, their anti-MRSA structure-activity relationships evaluated and selectivity versus human HKC-8 cells determined. Minimum inhibitory concentrations (MIC) ranged from 0.5 to 64 μg/mL and up to 16-fold selectivity was achieved. The 4-carbodithioate function was found to be essential for activity but non-specific reactivity was ruled out as a contributor to antibacterial action. The study supports further work aimed at elucidating the molecular targets of this interesting new class of anti-MRSA agents. |
| Databáze: | OpenAIRE |
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