Cytotoxic sugar analogues of an optimized novobiocin scaffold
Cytotoxic sugar analogues of an optimized novobiocin scaffold
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DOI：
10.1039/c0md00063a
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发表时间：
2010-08-01
期刊：
影响因子：
--
通讯作者：
Blagg, Brian S. J.
中科院分区：
文献类型：
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作者：
Donnelly, Alison C.;Zhao, Huiping;Blagg, Brian S. J.
对天然产物novobiocin的研究已经阐明了通过使novobiocin的糖附属物、香豆素核心和苯甲酰胺侧链多样化来增强对Hsp90抑制的特定修饰，已经合成了结构独特的支架。这些结构适应性已经产生了强大的细胞毒剂，例如KU135，它们的制备比那些含有novobiocin糖的化合物更简单。这些类似物已经被评估对两种癌细胞株的抑制作用，并显示出低微摩尔抗增殖活性。
Studies on the natural product, novobiocin, have elucidated specific modifications that increase Hsp90 inhibition Through diversification of the sugar appendage, coumarin core and benzamide side chain of novobiocin, structurally unique scaffolds have been synthesized These structural adaptations have produced potent cytotoxic agents, such as KU135, which are prepared more simply than those that contain the noviose sugar These analogues have been evaluated against two cancer cell lines and demonstrated low micromolar anti-proliferative activity