Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis.
Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis.
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DOI：
10.1021/acs.joc.7b01162
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发表时间：
2017-08-04
期刊：
影响因子：
--
通讯作者：
Movassaghi M
中科院分区：
文献类型：
--
作者：
Antropow AH;Xu K;Buchsbaum RJ;Movassaghi M
本文介绍了新的琼脂糖蛋白抑制素生物碱衍生物的合成及其在乳腺癌微环境中的抗癌评价。各种N1-烷基和C5-醚的agelastatin衍生物，通过应用我们的策略收敛咪唑酮合成从一个共同的硫酯沿着与适当取代的脲和醇组分。在我们的三维共培养试验中评价了这些琼脂糖蛋白衍生物对乳腺成纤维细胞对相关乳腺癌细胞的影响。我们已经发现，在非细胞毒性剂量下，Agelastatin生物碱是癌症侵袭和转移的有效调节剂。在此，我们讨论了（-）-agelastatin E与（-）-agelastatin A相比在此能力方面的增加的效力，此外还鉴定了具有与（-）-agelastatin E在统计学上等效的活性的新的agelastatin衍生物。本报告中描述的化学为快速合成作为癌症侵袭和转移调节剂的具有优异效力（50-100 nM）的agelastatin衍生物提供了平台。
The synthesis of new agelastatin alkaloid derivatives and their anticancer evaluation in the context of the breast cancer microenvironment is described. A variety of N1-alkyl and C5-ether agelastatin derivatives were accessed via application of our strategy for convergent imidazolone synthesis from a common thioester along with appropriately substituted urea and alcohol components. These agelastatin derivatives were evaluated in our three-dimensional co-culture assay for the effects of mammary fibroblasts on associated breast cancer cells. We have discovered that agelastatin alkaloids are potent modulators for cancer invasion and metastasis at non-cytotoxic doses. Herein we discuss the increased potency of (−)-agelastatin E as compared to (−)-agelastatin A in this capacity, in addition to identification of new agelastatin derivatives with activity that is statistically equivalent to (−)-agelastatin E. The chemistry described in this report provides a platform for the rapid synthesis of agelastatin derivatives with excellent potency (50–100 nM) as modulators for cancer invasion and metastasis.
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影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
DOI：
10.1039/c39930001305
发表时间：
1993-08-21
影响因子：
--
作者：
DAMBROSIO, M;GUERRIERO, A;PIETRA, F
通讯作者：
PIETRA, F
影响因子：
15
作者：
Feldman, KS;Saunders, JC
通讯作者：
Saunders, JC
影响因子：
4
作者：
Liu, Jiewei;Xu, Kun;Buchsbaum, Rachel J.
通讯作者：
Buchsbaum, Rachel J.
影响因子：
8.6
作者：
McClary B;Zinshteyn B;Meyer M;Jouanneau M;Pellegrino S;Yusupova G;Schuller A;Reyes JCP;Lu J;Guo Z;Ayinde S;Luo C;Dang Y;Romo D;Yusupov M;Green R;Liu JO
通讯作者：
Liu JO