Article
Development of a Highly Selective Plasmodium falciparum Proteasome Inhibitor with Anti-malaria Activity in Humanized Mice.
Natural Sciences and Mathematics | Faculty Scholarship
Department
Natural Sciences and Mathematics
Document Type
Article
Source
Angewandte Chemie International Edition
Publication Date
4-19-2021
Disciplines
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.
Citation Information
Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, et al.. "Development of a Highly Selective Plasmodium falciparum Proteasome Inhibitor with Anti-malaria Activity in Humanized Mice." Vol. 60 Iss. 17 (2021) p. 9279 - 9283 ISSN: 1521-3773 Available at: http://works.bepress.com/roland_cooper/72/