Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin‐Resistant Staphylococcus aureus (MRSA)
| العنوان: | Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin‐Resistant Staphylococcus aureus (MRSA) |
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| المؤلفون: | Warren R. J. D. Galloway, Naomi Robertson, Hannah F. Sore, Suzie Forrest, Sean Bartlett, Sarah L. Kidd, Julien J. Freudenreich, Martin Welch, David R. Spring |
| المصدر: | ChemMedChem. 15:1289-1293 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Methicillin-Resistant Staphylococcus aureus, Stereochemistry, Phenotypic screening, Microbial Sensitivity Tests, 010402 general chemistry, medicine.disease_cause, Metathesis, 01 natural sciences, Biochemistry, Structure-Activity Relationship, Ring-closing metathesis, Drug Discovery, medicine, Screening method, General Pharmacology, Toxicology and Pharmaceutics, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Chemistry, Organic Chemistry, Stereoisomerism, Methicillin-resistant Staphylococcus aureus, Anti-Bacterial Agents, 0104 chemical sciences, Staphylococcus aureus, Molecular Medicine, Antibacterial activity, Divergent synthesis |
| الوصف: | The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery. |
| تدمد: | 1860-7187 1860-7179 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e8a9006f3aeef817dbc1c5a9e8a0711 https://doi.org/10.1002/cmdc.202000179 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0e8a9006f3aeef817dbc1c5a9e8a0711 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18607187 18607179 |
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