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Publikācija: Azole-Based Non-Peptidomimetic Plasmepsin Inhibitors

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity EU Structural Funds
Defending: ,
Publication language English (en)
Title in original language Azole-Based Non-Peptidomimetic Plasmepsin Inhibitors
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors L. Kinena
G. Leitis
I. Kanepe-Lapsa
R. Bobrovs
Kristaps Jaudzems
V. Ozola
Edgars Sūna
Aigars Jirgensons
Keywords bioisosteric replacement, inhibitor, malaria | plasmepsins, Plasmodium falciparum, triazole
Abstract 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.
DOI: 10.1002/ardp.201800151
Reference Kinena, L., Leitis, G., Kanepe-Lapsa, I., Bobrovs, R., Jaudzems, K., Ozola, V., Sūna, E., Jirgensons, A. Azole-Based Non-Peptidomimetic Plasmepsin Inhibitors. Archiv der Pharmazie, 2018, Vol.351, pp.1800151a-1800151b. ISSN 0365-6233. Available from: doi:10.1002/ardp.201800151
Additional information Citation count:
ID 28471