Publications & Reports

A critical evaluation of pyrrolo[2,3-d]pyrimidine-4-amines as Plasmodium falciparum apical membrane antigen 1 (AMA1) inhibitors.

Devine SM, Lim SS, Chandrashekaran IR, MacRaild CA, Drew DR, Debono CO, Lam R, Anders RF, Beeson JG, Scanlon MJ, Scammellsa PJ, Norton RS


We have determined that a previously reported class of pyrrolo[2,3-d]pyrimidine-4-amines exhibit low binding to apical membrane antigen 1 (AMA1) and suffer from unattractive qualities, such as aggregation. We attempted to remove these traits by generating molecules with improved solubility, but this did not translate into enhanced binding affinity or inhibition of parasite growth in erythrocytes. These results indicate that anti-malarial activity is not primarily due to inhibition of AMA1 function, but mediated by an alternate or additional mechanism of action.


  • Journal: Medicinal Chemistry Communications
  • Published: 23/07/2014
  • Volume: Epub ahead of print


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