title: Nocardimicins G, H and I, siderophores with muscarinic M3 receptor binding inhibitory activity from Nocardia nova JCM 6044.
abstract: In the screening for muscarinic M3 receptor binding inhibitors from microbial secondary metabolites, the extract of Nocardia nova JCM 6044 was found to be highly active. Bioassay-guided isolation led to the identification of three siderophores, nocardimicins G (1), H (2) and I (3). Their chemical structures were determined by spectroscopic analysis using NMR and MS. 1 and 2 inhibited the binding of tritium-labeled N-methylscopolamine to the muscarinic M3 receptor with Ki values of 0.44 microM and 0.37 microM, respectively, whereas 3 showed no inhibition at 10 microM. 1 and 2 also showed weak binding inhibitory activity to the M5 receptor but not to the M1, M2 and M4 receptors at 10 microM.
authors.affiliation: Pharmaceuticals Research Unit, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan. ikeda.yoshitaka@mc.m-pharma.co.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Furumai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D006877:Hydroxamic Acids / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D009615:Nocardia / Q000737:chemistry*; D010080:Oxazoles / Q000302:isolation & purification / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017262:Siderophores / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D006877:Hydroxamic Acids; D018727:Muscarinic Antagonists; D010080:Oxazoles; D043587:Receptor, Muscarinic M3; D017262:Siderophores; C507227:nocardimicin G; C507226:nocardimicin H; C507228:nocardimicin I