Inhibition of the Non-Mevalonate Isoprenoid Pathway by Reverse Hydroxamate Analogues of Fosmidomycin

Claudia Lienau, Sarah Konzuch, Tobias Gräwert, Boris Illarionov, Adelbert Bacher, Markus Fischer, Nobutada Tanaka, Thomas Kurz
2015 Procedia Chemistry  
The non-mevalonate (methylerythritol phosphate, MEP) pathway for isoprenoid biosynthesis is essential in Plasmodium spp., but is absent in the human host. The pathway is a clinically validated antimalarial target on basis of studies with the antibiotic fosmidomycin, an inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr, IspC), which catalyses the first committed step of the MEP-pathway. In this review, we report on reverse, hydroxamate-based fosmidomycin analogues, which are
more » ... ues, which are studied by enzyme kinetics, parasite growth inhibition and crystallography in order to identify compounds with enhanced antiplasmodial activity. © 2015 C Lienau, S Konzuch, T Gräwert, B Illarionov, A Bacher, M Fischer, N Tanaka, T Kurz. Published by Elsevier B.V. Peer-review under responsibility of the Scientific Committee of HK-ICONS 2014.
doi:10.1016/j.proche.2015.03.016 fatcat:no4bibwp6ndxnioqb4hqbtzvsy