通过与非代谢糖缀合来增强环巴胺。
Enhancement of cyclopamine via conjugation with nonmetabolic sugars.
机构信息
Department of Chemistry, University of West Florida , 11000 University Parkway, Pensacola, Florida 32514, United States, and Center for Pharmaceutical Research and Innovation, University of Kentucky College of Pharmacy , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
出版信息
Org Lett. 2012 May 18;14(10):2454-7. doi: 10.1021/ol300703z. Epub 2012 Apr 27.
Abstract
The Veratrum alkaloid cyclopamine, an inhibitor of cancer stem cell growth, was used as a representative scaffold to evaluate the inhibitory impact of glycosylation with a group of nonmetabolic saccharides, such as d-threose. In a five-step divergent process, a 32-member glycoside library was created and assayed to determine that glycosides of such sugars notably improved the GI50 value of cyclopamine while metabolic sugars, such as d-glucose, did not.
摘要
白屈菜碱是一种抑制癌症干细胞生长的生物堿，被用作代表性支架，以评估一组非代谢糖，如 d-苏糖，对其进行糖基化的抑制作用。在一个五步发散过程中，创建了一个 32 成员的糖苷文库并进行了检测，结果表明，这些糖的糖苷显著提高了白屈菜堿的 GI50 值，而代谢糖，如 d-葡萄糖，则没有。
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本文引用的文献
1
Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules.酶法用于药物和小分子的糖基（多样化/随机化）。
Nat Prod Rep. 2011 Oct;28(11):1811-53. doi: 10.1039/c1np00045d. Epub 2011 Sep 8.
2
Warfarin glycosylation invokes a switch from anticoagulant to anticancer activity.华法林糖基化引发了从抗凝活性到抗癌活性的转变。
ChemMedChem. 2011 Aug 1;6(8):1347-50. doi: 10.1002/cmdc.201100178. Epub 2011 Jun 28.
3
Glycosyloxyamine neoglycosylation: a model study using calicheamicin.糖氧基胺新糖基化：使用刺孢霉素的模型研究
ChemMedChem. 2011 May 2;6(5):774-6. doi: 10.1002/cmdc.201100028. Epub 2011 Feb 23.
4
Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway.靶向 hedgehog 通路：环巴胺的开发和靶向 hedgehog 通路的抗癌药物的开发。
Mini Rev Med Chem. 2011 Mar;11(3):200-13. doi: 10.2174/138955711795049871.
5
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PLoS One. 2010 Dec 28;5(12):e15262. doi: 10.1371/journal.pone.0015262.
6
Carbohydrate-based bioactive compounds for medicinal chemistry applications.用于药物化学应用的基于碳水化合物的生物活性化合物。
Mini Rev Med Chem. 2011 Jan;11(1):39-54. doi: 10.2174/138955711793564060.
7
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