Department

Natural Sciences and Mathematics

Document Type

Article

Source

Angewandte Chemie International Edition

Publication Date

4-19-2021

ISSN

1521-3773

Volume

60

Issue

17

First Page

9279

Last Page

9283

Abstract

Plasmodium falciparum proteasome (Pf20S) inhibitors are active against Plasmodium at multiple stages-erythrocytic, gametocyte, liver, and gamete activation stages-indicating that selective Pf20S inhibitors possess the potential to be therapeutic, prophylactic, and transmission-blocking antimalarials. Starting from a reported compound, we developed a noncovalent, macrocyclic peptide inhibitor of the malarial proteasome with high species selectivity and improved pharmacokinetic properties. The compound demonstrates specific, time-dependent inhibition of the β5 subunit of the Pf20S, kills artemisinin-sensitive and artemisinin-resistant P. falciparum isolates in vitro and reduces parasitemia in humanized, P. falciparum-infected mice.

PubMed ID

33433953

Rights

© 2021 Wiley-VCH GmbH.

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