Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Design, synthesis and biological-activity of protaxols

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Nicolaou, K.C.
  • Riemer, C.
  • Kerr, M. A.
  • Rideout, D.
  • Wrasidlo, W.

publication date

  • July 1993

journal

  • Nature  Journal

abstract

  • Taxol is a product isolated from the Pacific yew tree (Taxus brevifolia) and is a potent microtubule-stabilizing agent which has recently been approved for treatment of otherwise intractable ovarian cancer. Despite taxol's therapeutic promise, its aqueous insolubility (< 0.004 mg ml-1) hampers its clinical application. Here we report the design, synthesis and biological activity of a series of taxol-releasing compounds (protaxols) with improved pharmacological properties. These prodrugs were designed to increase their aqueous solubility and allow for taxol release under basic or physiological conditions. We demonstrate the stability of these prodrugs at pH < or = 7 and their ability to release taxol in a basic medium. Taxol-like microtubule-stabilizing activity appears after the release of taxol. In vitro these prodrugs have cytotoxic properties against tumour cell lines comparable to those of taxol; moreover, human plasma catalyses the release of active taxol. These protaxols have greater potential as anticancer agents than the parent compounds taxol and taxotere (Fig. 1a).

subject areas

  • Animals
  • Cell Line
  • Chemistry, Pharmaceutical
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Humans
  • Microtubules
  • Paclitaxel
  • Prodrugs
  • Solubility
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/364464a0

PubMed ID

  • 8101355
scroll to property group menus

Additional Document Info

start page

  • 464

end page

  • 466

volume

  • 364

issue

  • 6436

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support