Semisynthesis of novel monacolin J derivatives: hypocholesterolemic and neuroprotective activities

The Journal of Antibiotics
Sonia CampoyJose L Adrio

Abstract

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.

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Citations

Jun 14, 2016·Expert Review of Neurotherapeutics·William James Deardorff, George T Grossberg

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