Synthesis and biological evaluation of arylated novobiocin analogs as Hsp90 inhibitors.

Abstract

Novobiocin analogs lacking labile glycosidic ether have been designed, synthesized and evaluated for Hsp90 inhibitory activity. Replacement of the synthetically complex noviose sugar with simple aromatic side chains produced analogs that maintain moderate cytotoxic activity against MCF7 and SkBR3 breast cancer cell-lines. Rationale for the preparation of des-noviose novobiocin analogs in addition to their synthesis and biological evaluation are presented herein.

• Authors: Bhaskar Reddy Kusuma, Adam S Duerfeldt, Brian S J Blagg
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 23 Pg. 7170-4 (Dec 01 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 22014546 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• HSP90 Heat-Shock Proteins
• Novobiocin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Molecular Structure
• Novobiocin (chemical synthesis, chemistry, pharmacology)