Azole-based non-peptidomimetic plasmepsin inhibitors.

Autor: Kinena L; Latvian Institute of Organic Synthesis, Riga, Latvia., Leitis G; Latvian Institute of Organic Synthesis, Riga, Latvia., Kanepe-Lapsa I; Latvian Institute of Organic Synthesis, Riga, Latvia., Bobrovs R; Latvian Institute of Organic Synthesis, Riga, Latvia., Jaudzems K; Latvian Institute of Organic Synthesis, Riga, Latvia., Ozola V; Latvian Institute of Organic Synthesis, Riga, Latvia., Suna E; Latvian Institute of Organic Synthesis, Riga, Latvia., Jirgensons A; Latvian Institute of Organic Synthesis, Riga, Latvia.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2018 Sep; Vol. 351 (9), pp. e1800151. Date of Electronic Publication: 2018 Jul 31.
DOI: 10.1002/ardp.201800151
Abstrakt: The spread of drug-resistant malaria parasites urges the search for new antimalarial drugs. Malarial aspartic proteases - plasmepsins (Plms) - are differentially expressed in multiple stages of the Plasmodium parasite's lifecycle and are considered as attractive drug targets. We report the development of novel azole-based non-peptidomimetic plasmepsin inhibitors that have been designed by bioisosteric substitution of the amide moiety in the Actelion amino-piperazine inhibitors. The best triazole-based inhibitors show submicromolar potency toward Plm II, which is comparable to that of the parent Actelion compounds. The new inhibitors can be used as a starting point for the development of a resistance-free antimalarial drug targeting the non-digestive Plm IX or X, which are essential for the malaria parasite life cycle.
(© 2018 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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