title: 3D-QSAR Assisted Design, Synthesis and Evaluation of Novobiocin Analogues.
abstract: Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure-activity relationships. Based upon the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure-activity (3D-QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D-QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced anti-proliferative activity at mid nano-molar concentrations, which results through Hsp90 inhibition.
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045-7563, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhao
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
keywords: 3D-QSAR; Breast cancer; Heat shock protein 90; Hsp90 inhibitors; Novobiocin