title: 3-normeridamycin: a potent non-immunosuppressive immunophilin ligand is neuroprotective in dopaminergic neurons.
abstract: 3-Normeridamycin (1), isolated from fermentation extracts of the soil actinomycete Streptomyces sp. LL-C31037, demonstrated potent neuroprotective activity. When challenged with the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), known to induce parkinsonism, 1 restored functional dopamine uptake in a concentration-dependent manner, with an EC50 of 110 nM in dopaminergic neurons. The structure of 1 was determined via spectroscopic methods, and the immunosuppressive and immunophilin binding properties of the compound were also measured.
authors.affiliation: Department of Chemical & Screening Sciences, Wyeth Research, 401 N. Middletown Rd., Pearl River, NY 10965, USA.
authors.forename: Mia Y
authors.initials: MY
authors.lastname: Summers
authors.forename: Margaret
authors.initials: M
authors.lastname: Leighton
authors.forename: Danni
authors.initials: D
authors.lastname: Liu
authors.forename: Kevin
authors.initials: K
authors.lastname: Pong
authors.forename: Edmund I
authors.initials: EI
authors.lastname: Graziani
mesh_terms: D000978:Antiparkinson Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D020104:Immunophilins / Q000378:metabolism*; D008024:Ligands; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*
chemical_list: C511079:3-normeridamycin; D000978:Antiparkinson Agents; D008024:Ligands; D018942:Macrolides; D018696:Neuroprotective Agents; D020104:Immunophilins