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

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

  • ACS Med Chem Lett. 2012 Jan 1;4(1):57-62. doi: 10.1021/ml300275g.
Huiping Zhao 1,  Elisabetta Moroni,  Bin Yan,  Giorgio Colombo,  Brian S J Blagg
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045-7563, USA.
PMID: 23606927 DOI: 10.1021/ml300275g
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.

Keywords

3D-QSAR; Breast cancer; Heat shock protein 90; Hsp90 inhibitors; Novobiocin.

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