Christopher Arico-Muendela; Paolo A. Centrella; Brooke D. Contonio; Barry A. Morgan; Gary O’Donovan; Christopher L. Paradise; Steven R. Skinner; Barbara Sluboski; Jennifer L. Svendsen; Kerry F. White; Anjan Debnath; Jiri Gut; Nathan Wilson; James H. McKerrow; Joseph L. DeRisi; Philip J. Rosenthal; Peter K. Chiang
Bioorg. Med. Chem. Lett., 2009, 19, 19, 5128-5131
https://doi.org/10.1016/j.bmcl.2009.07.029

Abstract

Fumagillin, an irreversible inhibitor of MetAP2, has been shown to potently inhibit growth of malaria parasites in vitro. Here, we demonstrate activity of fumagillin analogs with an improved pharmacokinetic profile against malaria parasites, trypanosomes, and amoebas. A subset of the compounds showed efficacy in a murine malaria model. The observed SAR forms a basis for further optimization of fumagillin based inhibitors against parasitic targets by inhibition of MetAP2.