Azole-Based Non-Peptidomimetic Plasmepsin Inhibitors
Archiv der Pharmazie 2018
L. Kinena, G. Leitis, I. Kanepe-Lapsa, R. Bobrovs, Kristaps Jaudzems, V. Ozola, Edgars Sūna, Aigars Jirgensons

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.


Atslēgas vārdi
bioisosteric replacement, inhibitor, malaria | plasmepsins, Plasmodium falciparum, triazole
DOI
10.1002/ardp.201800151

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, 1800151a.-1800151b.lpp. ISSN 0365-6233. Pieejams: doi:10.1002/ardp.201800151

Publikācijas valoda
English (en)
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