Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Kato, Hikaru¹  Kai, Aika¹  Kawabata, Tetsuro¹  Sunderhaus, James D.²  McAfoos, Timothy J.²  Finefield, Jennifer M.²  Sugimoto, Yukihiko³  Williams, Robert M.^2,4  Tsukamoto, Sachiko¹ 

[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Nat Prod, Oe Honmachi 5-1, Kumamoto 8620973, Japan

[2] Colorado State Univ, Dept Chem, 1301 Ctr Ave, Ft Collins, CO 80523 USA

[3] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Biochem, Oe Honmachi 5-1, Kumamoto 8620973, Japan

[4] Univ Colorado, Canc Ctr, Aurora, CO 80045 USA

关键词: Notoamide;    Enantiomer;    Osteoclastogenesis;    Aspergillus;    Fungus;   

DOI  :  10.1016/j.bmcl.2017.10.017

来源: Elsevier

【 摘 要 】

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (-)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (-)-6-epi-notoamide T was the most potent inhibitor with an IC50 value of 1.7 mu M. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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