title: Semisynthesis of novel monacolin J derivatives: hypocholesterolemic and neuroprotective activities.
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.
authors.affiliation: BioIndustrial Division, Neuron BPh, Granada, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Campoy
authors.forename: Saleta
authors.initials: S
authors.lastname: Sierra
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suarez
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ramos
authors.forename: Javier
authors.initials: J
authors.lastname: Velasco
authors.forename: Javier S
authors.initials: JS
authors.lastname: Burgos
authors.forename: Jose L
authors.initials: JL
authors.lastname: Adrio
mesh_terms: D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000378:metabolism*; D005658:Fungi / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D009153:Mutagens; D009281:Naphthalenes; D018696:Neuroprotective Agents; D008769:Methylnitronitrosoguanidine; D006903:Hydroxymethylglutaryl CoA Reductases; C045376:monacolin J