title: Neolignans from the Arils of Myristica fragrans as Potent Antagonists of CC Chemokine Receptor 3.
abstract: CC chemokine receptor 3 (CCR3) is expressed selectively in eosinophils, basophils, and some Th2 cells and plays a major role in allergic diseases. A methanol extract from the arils of Myristica fragrans inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 μg/mL. From this extract, eight new neolignans, maceneolignans A-H (1-8), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds 1, 4, 6, and 8 and (+)-erythro-(7S,8R)-Δ(8')-7-hydroxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (11), (-)-(8R)-Δ(8')-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (17), (+)-licarin A (20), nectandrin B (25), verrucosin (26), and myristicin (27) inhibited CCR3-mediated chemotaxis at a concentration of 1 μM. Among them, 1 (EC50 1.6 μM), 6 (1.5 μM), and 8 (1.4 μM) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 μM).
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hachiman
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuo
authors.forename: Eriko
authors.initials: E
authors.lastname: Nishida
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Faculty of Medicine, Kindai University , 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D002633:Chemotaxis / Q000187:drug effects; D004804:Eosinophils / Q000378:metabolism; D005663:Furans / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D026323:Myristica / Q000737:chemistry*; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D005663:Furans; D017705:Lignans; D054397:Receptors, CCR3; C524653:nectandrin-B; C561302:verrucosin