Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain

Roberta Ettari; Maria Zappalà; Nicola Micale; Tanja Schirmeister; Christoph Gelhaus; Matthias Leippe; Astrid Evers; Silvana Grasso

doi:10.1016/j.ejmech.2010.04.003

Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain

Eur J Med Chem. 2010 Jul;45(7):3228-33. doi: 10.1016/j.ejmech.2010.04.003. Epub 2010 Apr 14.

Authors

Roberta Ettari¹, Maria Zappalà, Nicola Micale, Tanja Schirmeister, Christoph Gelhaus, Matthias Leippe, Astrid Evers, Silvana Grasso

Affiliation

¹ Dipartimento Farmaco-Chimico, University of Messina, Viale Annunziata, 98168 Messina, Italy. [email protected]

PMID: 20434817
DOI: 10.1016/j.ejmech.2010.04.003

Abstract

This paper describes the synthesis of novel peptidomimetics bearing a protected aspartyl aldeyde warhead leading to the thioacylals 2a,b and the acylals 3a,b. Compounds 2a and 3a proved to possess an increased antiplasmodial activity with respect to the parent molecule 1. Furthermore thioacylal 2a can be considered as a promising trypanocidal agent.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cysteine Endopeptidases / metabolism*
Humans
Inhibitory Concentration 50
Peptides / chemical synthesis
Peptides / chemistry*
Peptides / pharmacology*
Plasmodium falciparum / enzymology*
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Substrate Specificity

Substances

Peptides
Protease Inhibitors
Cysteine Endopeptidases
falcipain 2
rhodesain