Synthesis and biological evaluation of functionalised tetrahydro-β-carboline analogues as inhibitors of Toxoplasma gondii invasion

Jeffrey G. A. Walton; Stephen Patterson; Gu Liu; Jeralyn D. Haraldsen; Jonathan J. Hollick; Alexandra M. Z. Slawin; Gary E. Ward; Nicholas J. Westwood

doi:10.1039/B902319D

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Organic & Biomolecular Chemistry

Issue 15, 2009

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Synthesis and biological evaluation of functionalised tetrahydro-β-carboline analogues as inhibitors of Toxoplasma gondii invasion

Jeffrey G. A. Walton , Stephen Patterson , Gu Liu , Jeralyn D. Haraldsen , Jonathan J. Hollick , Alexandra M. Z. Slawin , Gary E. Ward and Nicholas J. Westwood

Org. Biomol. Chem., 2009, 7, 3049-3060

DOI: 10.1039/B902319D
Received 04 Feb 2009, Accepted 22 May 2009
First published on the web 17 Jun 2009

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Techniques for the identification of the protein target(s) of small molecules are proving very important following an increase in the use of phenotype-based screening in chemical biology and drug discovery. One approach, known as the yeast-3-hybrid approach, has shown considerable potential. A key factor in the success of this approach is the preparation of a complex molecule referred to as a chemical inducer of dimerisation (CID). The synthesis of two CIDs based on a bioactive tetrahydro-β-carboline core structure is reported and evidence presented that shows the CIDs are of utility in this approach. A series of chemo- and bioinformatic studies coupled with SAR development inspired the choice of CIDs.

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Jeffrey G. A. Walton
Stephen Patterson
Gu Liu
Jeralyn D. Haraldsen
Jonathan J. Hollick
Alexandra M. Z. Slawin
Gary E. Ward
Nicholas J. Westwood

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Organic & Biomolecular Chemistry

Synthesis and biological evaluation of functionalised tetrahydro-β-carboline analogues as inhibitors of Toxoplasma gondii invasion

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