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

Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts.
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DOI:
10.1016/j.bmcl.2017.10.017
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发表时间:
2017-11-15
影响因子:
2.7
通讯作者:
Tsukamoto S
Tsukamoto S
中科院分区:
医学4区
文献类型:
--
作者:
Kato H;Kai A;Kawabata T;Sunderhaus JD;McAfoos TJ;Finefield JM;Sugimoto Y;Williams RM;Tsukamoto S

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海洋来源的隆突曲霉(Aspergillusproubulus)MF 297 -2和陆地来源的A. amoenus NRRL 35600产生对映体异戊二烯化吲哚生物碱。天然和合成衍生物的生物活性研究表明,与相应的(+)-对映体相比,三七酰胺A和B的(-)-对映体、6-表-三七酰胺T和千金藤素A更强地抑制核因子-κB(NF-κB)配体受体激活剂(RANKL)诱导的小鼠RAW 264细胞破骨细胞分化。其中,(−)-6-epi-notoamide T是最有效的抑制剂,IC 50值为1.7 μM。
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-κB (NF-κB) 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 μM.
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