A polybromodiphenyl ether from an Indonesian marine sponge Lamellodysidea herbacea and its chemical derivatives inhibit protein tyrosine phosphatase 1B, an important target for diabetes treatment.
A polybromodiphenyl ether from an Indonesian marine sponge Lamellodysidea herbacea and its chemical derivatives inhibit protein tyrosine phosphatase 1B, an important target for diabetes treatment.
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DOI：
10.1007/s11418-012-0735-y
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发表时间：
2013-10
影响因子：
3.3
通讯作者：
Namikoshi, Michio
中科院分区：
文献类型：
--
作者：
Yamazaki, Hiroyuki;Sumilat, Deiske A.;Kanno, Syu-ichi;Ukai, Kazuyo;Rotinsulu, Henki;Wewengkang, Defny S.;Ishikawa, Masaaki;Mangindaan, Remy E. P.;Namikoshi, Michio
关键词：
印度尼西亚海洋海绵Lamellodysideaherbacea的乙醇提取物抑制蛋白酪氨酸磷酸酶1B（PTP 1B）的活性，PTP 1B是治疗II型糖尿病的重要靶酶。生物测定引导的分离产生了一种已知的多溴二苯醚（1），作为唯一的生物活性成分。化合物1及其甲醚衍生物（2）的光谱数据证实了化合物1的结构。化合物1显著抑制PTP 1B活性（IC 50 = 0.85 μM），并显示出对两种人癌细胞系HCT-15（结肠）和Jurkat（T细胞淋巴瘤）细胞的中等细胞毒性。另一方面，化合物2保持对PTP 1B的有效抑制活性（IC 50 = 1.7 μM），但在18 μM下对这些癌细胞没有显示出明显的细胞毒性。从1制备了四种酯衍生物[乙酰基（3）、丁酰基（4）、己酰基（5）和苯甲酰基（6）]，并评价了它们对PTP 1B和两种癌细胞系的活性，以研究结构-活性关系。虽然化合物3-6显示出对PTP 1B活性的有效抑制作用，但观察到对HCT-15和Jurkat细胞的细胞毒性与1的效果相似。从这些结果中，发现化合物2是PTP 1B的最佳抑制剂，没有明显的细胞毒性。因此，2可能是制备新型PTP 1B抑制剂的先导化合物。此外，化合物2不抑制Huh-7细胞（肝癌）的细胞生长。肝细胞是PTP 1B的位置之一，Huh-7细胞用于研究化合物2的作用机制。
The ethanol extract of an Indonesian marine sponge Lamellodysidea herbacea inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), an important target enzyme for the treatment of type II diabetes. Bioassay-guided isolation yielded a known polybromodiphenyl ether (1) as a sole bioactive component. The structure of 1 was confirmed by spectroscopic data for 1 and its methyl ether derivative (2). Compound 1 markedly inhibited the PTP1B activity (IC50 = 0.85 μM) and showed a moderate cytotoxicity against two human cancer cell lines, HCT-15 (colon) and Jurkat (T-cell lymphoma) cells. On the other hand, compound 2 maintained potent inhibitory activity against PTP1B (IC50 = 1.7 μM) but did not show apparent cytotoxicity at 18 μM against these cancer cells. Four ester derivatives [acetyl (3), butyryl (4), hexanoyl (5), and benzoyl (6)] were prepared from 1 and their activities evaluated against PTP1B and two cancer cell lines to investigate the structure–activity relationships. Although compounds 3–6 exhibited potent inhibitory effects against PTP1B activity, cytotoxicity against HCT-15 and Jurkat cells was observed as a similar efficacy to that of 1. From these results, compound 2 was found to be the best inhibitor of PTP1B with no apparent cytotoxicity. Therefore, 2 may be a lead compound for making a new type of PTP1B inhibitor. Moreover, compound 2 did not inhibit the cell growth of Huh-7 cells (hepatoma). Hepatocytes are one of the locations of PTP1B, and Huh-7 cells are used to study the mechanism of action of compound 2.
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影响因子：
7.7
作者：
González-Rodríguez A;Mas Gutierrez JA;Sanz-González S;Ros M;Burks DJ;Valverde AM
通讯作者：
Valverde AM
影响因子：
5.1
作者：
Liu, HW;Namikoshi, M;Yao, XS
通讯作者：
Yao, XS
影响因子：
4.8
作者：
AHMAD, F;LI, PM;GOLDSTEIN, BJ
通讯作者：
GOLDSTEIN, BJ
DOI：
10.1016/j.bbrc.2007.06.130
发表时间：
2007-11-03
影响因子：
3.1
作者：
Sato, Hiroyuki;Genet, Cedric;Saladin, Regis
通讯作者：
Saladin, Regis
齐墩果酸及其衍生物：具有细胞活性的新型蛋白酪氨酸磷酸酶1B抑制剂
影响因子：
3.5
作者：
Zhang, Yi-Nan;Zhang, Wei;Hu, Li-Hong
通讯作者：
Hu, Li-Hong