Abstract
Apicularens A and B were isolated from the myxobacterial genus Chondromyces apiculatus JW184. Apicularen A inhibited bafilomycin A1-sensitive ATP-dependent proton transport into microsome vesicles more potently than apicularen B. Bone resorption in cultures of mouse calvariae induced by human parathyroid hormone (PTH) or interleukin-1β (IL-1β) was inhibited by apicularen A at 10 and 100 nM, while apicularen B had no effect. The bisphosphonate incadronate inhibited bone resorption at 100 nM, being less effective than apicularen A. Our findings indicate that apicularen A inhibits bone resorption induced by PTH or IL-1β more potently than apicularen B, probably due to inhibition of the V-ATPase.
References
-
1
Kunze B, Jansen R, Sasse F, Höfle G, Reichenbach H.
Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties.
J Antibiot.
1998;
51
1075-80
-
2
Bhattacharjee A, Sequil O R, De Brabander J K.
Total synthesis and biological evaluation of apicularen A and synthetic analogs.
Tetrahedron Lett.
2001;
42
1217-20.
-
3
Huss M, Sasse F, Kunze B, Jansen R, Steinmetz H, Ingenhorst G. et al .
Archazolid and apicularen: novel specific V-ATPase inhibitors.
BMC Biochem.
2005;
6
13-22
-
4
Blair H C, Teitelbaum S L, Ghiselli R, Gluck S.
Osteoclastic bone resorption by a polarized vacuolar proton pump.
Science.
1989;
245
855-7
-
5
Sundquist K, Lakkakorpi P, Wallmark B, Väänänen K.
Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption.
Biochem Biophys Res Commun.
1990;
168
309-13
-
6
Hong J, Ishihara K, Zee O, Ohuchi K.
Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60.
Planta Med.
2005;
71
306-12
-
7
Hong J, Yokomakura A, Nakano Y, Ban H S, Ishihara K, Ahn J W. et al .
Induction of nitric oxide production by the cytostatic macrolide apicularen A [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14-dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1-propenyl], (2Z,4Z)-(9CI)] and possible role of nitric oxide in apicularen A-induced apoptosis in RAW 264.7 cells.
J Pharmacol Exp Ther.
2005;
312
968-77
-
8
Niikura K, Takeshita N, Takano M.
A vacuolar ATPase inhibitor, FR167356, prevents bone resorption in ovariectomized rats with high potency and specificity: potential for clinical application.
J Bone Miner Res.
2005;
20
1579-88
-
9
Hong J, Yamaki K, Ishihara K, Ahn J W, Zee O, Ohuchi K.
Induction of apoptosis RAW 264.7 cells by the cytostatic macrolide apicularen A.
J Pharm Pharmacol.
2003;
55
1299-306
Prof. Dr. Kazuo Ohuchi
Laboratory of Pathophysiological Biochemistry
Graduate School of Pharmaceutical Sciences
Tohoku University
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