1281869-67-7Relevant academic research and scientific papers
Engineering an antibiotic to fight cancer: Optimization of the novobiocin scaffold to produce anti-proliferative agents
Zhao, Huiping,Donnelly, Alison C.,Kusuma, Bhaskar R.,Brandt, Gary E. L.,Brown, Douglas,Rajewski, Roger A.,Vielhauer, George,Holzbeierlein, Jeffrey,Cohen, Mark S.,Blagg, Brian S. J.
, p. 3839 - 3853 (2011/09/13)
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 midnanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition.
