title: Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors.
abstract: Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued.
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hall
authors.affiliation: Department of Urology, The University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 1016, Kansas City, KS 66160, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Brown
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Brandes
authors.affiliation: Department of Pharmaceutical Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bazzill
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 1016, Kansas City, KS 66160, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Grogan
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Chitra
authors.initials: C
authors.lastname: Subramanian
authors.affiliation: Department of Urology, The University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 1016, Kansas City, KS 66160, USA.
authors.forename: George
authors.initials: G
authors.lastname: Vielhauer
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Pharmaceutical Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 1016, Kansas City, KS 66160, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cohen
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
keywords: Breast cancer; Heat shock protein 90; Hsp90 C-terminal inhibitors; Novobiocin; Triazole