Nocardimicins G, H and I, siderophores with muscarinic M3 receptor binding inhibitory activity from Nocardia nova JCM 6044.
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.
Ikeda
Yoshitaka
Y
Pharmaceuticals Research Unit, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan. ikeda.yoshitaka@mc.m-pharma.co.jp
Furumai
Tamotsu
T
Igarashi
Yasuhiro
Y
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
D006877:Hydroxamic Acids; D018727:Muscarinic Antagonists; D010080:Oxazoles; D043587:Receptor, Muscarinic M3; D017262:Siderophores; C507227:nocardimicin G; C507226:nocardimicin H; C507228:nocardimicin I