University of Vermont

Synthesis and Biological Evaluation of Functionalised Tetrahydro-B-carboline Analogues as Inhibitors of Toxoplasma gondii Invasion


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-beta-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.

Org Biomol Chem 15:3049-3060