Identification and Characterization of Novel Antimitotic Compounds for the Treatment of Breast Cancer

Abstract

Our goal is to find new antimitotic drugs for the treatment of breast cancer using a novel cell-based assay to screen natural product libraries and guide the purification of their active components. In year 1, we carried out a screen of over 30,000 extracts of terrestrial plants, algae and marine organisms, obtained 223 positive extracts, and isolated and identified active compounds from S of the positive extracts. In year 2, we isolated several new analogs of the microtubule-stabilizing compound eleutherobin and produced several more by synthetic transformation. We used the analogs to carry out an extended structure-activity relationship study of eleutherobin and identified unanticipated structural requirements that will be important for future pharmacophore models. We have also isolated sufficient amounts of eleutherobin and desmethyleleutherobin for in vivo testing. We isolated active compounds from 5 additional extracts, 3 of which have novel mechanisms of action that are currently under investigation.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2001
Accession Number
ADA396413

Entities

People

  • Michel Roberge

Organizations

  • University of British Columbia

Tags

DTIC Thesaurus Topics

  • Alkenes
  • Aquatic Organisms
  • Biochemistry
  • Biological Products
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Fungi
  • Identification
  • Materials
  • Molecular Biology
  • Neoplasms
  • Organic Chemistry

Readers

  • Marine Ecotoxicology
  • Molecular and Cellular Biochemistry