Horticulture Commons^™

High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge As Inhibitors Of Plasmodium Falciparum, Sandra Johannsen, Robin M. Gierse, Arne KrüGer, Rachel L. Edwards, Vittoria Nanna, Anna Fontana, Di Zhu, Tiziana Masini, Lais Pessanha De Carvalho, Mael Poizat, Bart Kieftenbelt, Dana M. Hodge, Sophie University Of Nebraska-Lincoln,, Daan Bunt, Antoine Lacour, Atanaz Shams, Kamila Anna Meissner, Edmarcia Elisa De Souza, Melloney Dröge, Bernard Van Vliet, Jack Den Hartog, Michael C. Hutter, Jana Held, Audrey R. Odom John, Carsten Wrenger, Anna K.H. Hirsch

Department of Agronomy and Horticulture: Faculty Publications

In this study, we identified three novel compound classes with potent activity against Plasmodium falciparum, the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing, and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-D-xylulose-5- phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against Mycobacterium tuberculosis. The close structural similarities of the active sites of the DXPS enzymes of P. falciparum and M. tuberculosis prompted investigation of their antiparasitic action, all classes …