Engineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents.
Engineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents.
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DOI：
10.1021/jm200148p
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发表时间：
2011-06-09
影响因子：
7.3
通讯作者：
Blagg BS
中科院分区：
文献类型：
--
作者：
Zhao H;Donnelly AC;Kusuma BR;Brandt GE;Brown D;Rajewski RA;Vielhauer G;Holzbeierlein J;Cohen MS;Blagg BS
DNA旋转酶抑制剂novobiocin是通过对酰胺侧链、香豆素环和糖基进行结构修饰而成为选择性Hsp90抑制剂的。根据对乳腺、结肠、前列腺、肺和其他癌细胞株的细胞效率的评估，这些物种的抗增殖活性比天然产品提高了约700倍。利用为三个新生物素合成子建立的结构-活性关系，产生了优化的支架，这些支架显示出对一组癌细胞的中纳米分子活性，并作为先导化合物，通过抑制Hsp90来显示其活性。
Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition.
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影响因子：
4.2
作者：
Peterson LB;Blagg BS
通讯作者：
Blagg BS
影响因子：
50.3
作者：
Isaacs, JS;Xu, WP;Neckers, L
通讯作者：
Neckers, L
影响因子：
--
作者：
Donnelly, Alison C.;Zhao, Huiping;Blagg, Brian S. J.
通讯作者：
Blagg, Brian S. J.
影响因子：
3.6
作者：
Donnelly, Alison C.;Mays, Jared R.;Burlison, Joseph A.;Nelson, John T.;Vielhauer, George;Holzbeierlein, Jeffrey;Blagg, Brian S. J.
通讯作者：
Blagg, Brian S. J.
影响因子：
3.6
作者：
Shelton, Shary N.;Shawgo, Mary E.;Robertson, John D.
通讯作者：
Robertson, John D.