Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674.
In the screening for muscarinic M3 receptor binding inhibitors from microbial secondary metabolites, the extract of Nocardia sp. TP-A0674 was found to be highly active. Bioassay-guided fractionation of it led to the isolation of six new siderophores, nocardimicins A (1), B (2), C (3), D (4), E (5), and F (6), as active principles. Their chemical structures were determined by spectroscopic and degradation analysis. Of these congeners, nocardimicin B (2) inhibited the binding of tritium-labeled N-methylscopolamine to the muscarinic M3 receptor most potently with a Ki value of 0.13 microM. Compound 2 showed more selective activity to M3 and M4 receptors than other subtypes.
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
Nonaka
Hikaru
H
Furumai
Tamotsu
T
Onaka
Hiroyasu
H
Igarashi
Yasuhiro
Y
D006801:Humans; D007564:Japan; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D009615:Nocardia / Q000737:chemistry*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D017262:Siderophores / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D017262:Siderophores