Semisynthesis of novel monacolin J derivatives: hypocholesterolemic and neuroprotective activities
| Autor: | Saleta Sierra, Javier S. Burgos, Sonia Campoy, Beatriz Suárez, Maria da Conceição Klaus V. Ramos, José L. Adrio, Javier Velasco |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Pharmacology
Antifungal Methylnitronitrosoguanidine medicine.drug_class Anticholesteremic Agents Fungi Naphthalenes Biology Neuroprotection Semisynthesis Beta-lactam Inhibitory Concentration 50 chemistry.chemical_compound Neuroprotective Agents chemistry Biochemistry Mutation Drug Discovery Monacolin J medicine Humans Hydroxymethylglutaryl CoA Reductases Mutagens |
| Zdroj: | The Journal of Antibiotics. 63:499-505 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.1038/ja.2010.76 |
| Popis: | A fungal strain able to naturally accumulate large amounts of monacolin J was improved by N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis and genetic disruption of the lovF gene. Semisynthesis was then used to produce novel statins by attaching different side chains at the C8 hydroxyl residue. In vitro hypocholesterolemic and neuroprotection assays showed that one derivative (NST0037) had a very low 3-hydroxy-3-methylglutaryl CoA reductase IC(50) and high protection rate for oxidative-stress-induced neuron cell death. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|