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

Xudong Geng; Raphaël Geney; Paula Pera; Ralph J Bernacki; Iwao Ojima

doi:10.1016/j.bmcl.2004.04.060

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.

Authors

Xudong Geng¹, Raphaël Geney, Paula Pera, Ralph J Bernacki, Iwao Ojima

Affiliation

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Alkaloids / chemical synthesis*
Alkaloids / pharmacology
Antineoplastic Agents, Phytogenic / chemical synthesis*
Antineoplastic Agents, Phytogenic / pharmacology
Bridged Bicyclo Compounds / chemistry
Drug Design
Humans
Inhibitory Concentration 50
Molecular Conformation
Molecular Mimicry
Structure-Activity Relationship
Taxoids / chemistry*
Taxoids / pharmacology
Tumor Cells, Cultured

Substances

Alkaloids
Antineoplastic Agents, Phytogenic
Bridged Bicyclo Compounds
Taxoids