Development of inhibitors of Plasmodium falciparum apical membrane antigen 1 based on fragment screening

San Sui Lim, Cael Debono, Christopher Andrew MacRaild, Indu Rajmohan Chandrashekaran, Olan Dolezal, Robin F Anders, Jamie Scott Simpson, Martin Scanlon, Shane Devine, Peter John Scammells, Raymond Stanley Norton

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21 Citations (Scopus)


Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 . The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.
Original languageEnglish
Pages (from-to)1530 - 1536
Number of pages7
JournalAustralian Journal of Chemistry
Issue number12
Publication statusPublished - 2013

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