biostudies-literatureZhao HNCI NIH HHS3839-53https://www.ebi.ac.uk/biostudies/studies/S-EPMC3164572biostudies-literatureUnknown54(11)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.Journal of medicinal chemistryEngineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents.PMC3164572U01 CA120458U01 CA120458-05R01 CA120458CA120458Brandt GERajewski RABlagg BSKusuma BRVielhauer GHolzbeierlein JDonnelly ACBrown DCohen MSZhao HfalseEngineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents.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.2011-01-01T00:00:00Z2011 Jun2024-10-17T15:03:48.892Z2019-03-27T00:43:30ZS-EPMC31645722155382210.1021/jm200148p