Design and synthesis of de novo cytotoxic alkaloids through mimicking taxoid skeleton

  • Bioorg Med Chem Lett. 2004 Jul 5;14(13):3491-4. doi: 10.1016/j.bmcl.2004.04.060.
Xudong Geng  1 ,  Raphaël Geney ,  Paula Pera ,  Ralph J Bernacki ,  Iwao Ojima
Affiliations
  • 1. Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
PMID: 15177459 DOI: 10.1016/j.bmcl.2004.04.060
Abstract

Based on a common pharmacophore model and the hypothesis that the baccatin core of taxoids is a scaffold securing the proper orientation of the side chains, a bicyclic alkaloid scaffold was designed as a baccatin surrogate. Using this scaffold, two novel macrocyclic and open-chain 'taxoid-mimicking' compounds were synthesized. Two of these 'taxoid-mimics', 2 and 3, were found to possess cytotoxicity with micromolar level IC50 values against human breast Cancer cell lines.