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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.

SUBMITTER: Zhao H

PROVIDER: S-EPMC3627542 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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3D-QSAR Assisted Design, Synthesis and Evaluation of Novobiocin Analogues.

Zhao Huiping H Moroni Elisabetta E Yan Bin B Colombo Giorgio G Blagg Brian S J BS

ACS medicinal chemistry letters 20120101 1

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 structu ...[more]

PMID: 23606927

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