New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies

MMV’s Malaria Box compound MMV030666 shows multi-stage activity against various strains of Plasmodium falciparum and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A...

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Autores principales: Hermann, Theresa, Wallner, Robin, Dolensky, Johanna, Seebacher, Werner, Pferschy-Wenzig, Eva-Maria, Kaiser, Marcel, Mäser, Pascal, Weis, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783227/
https://www.ncbi.nlm.nih.gov/pubmed/36558954
http://dx.doi.org/10.3390/ph15121503
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author Hermann, Theresa
Wallner, Robin
Dolensky, Johanna
Seebacher, Werner
Pferschy-Wenzig, Eva-Maria
Kaiser, Marcel
Mäser, Pascal
Weis, Robert
author_facet Hermann, Theresa
Wallner, Robin
Dolensky, Johanna
Seebacher, Werner
Pferschy-Wenzig, Eva-Maria
Kaiser, Marcel
Mäser, Pascal
Weis, Robert
author_sort Hermann, Theresa
collection PubMed
description MMV’s Malaria Box compound MMV030666 shows multi-stage activity against various strains of Plasmodium falciparum and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed. Physicochemical and pharmacokinetic parameters were determined experimentally (passive permeability) or calculated. Compared to the lead compound a diarylthioether was more active and less cytotoxic resulting in an excellent selectivity index of 850. In addition, pharmacokinetic and physicochemical parameters were improved.
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spelling pubmed-97832272022-12-24 New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies Hermann, Theresa Wallner, Robin Dolensky, Johanna Seebacher, Werner Pferschy-Wenzig, Eva-Maria Kaiser, Marcel Mäser, Pascal Weis, Robert Pharmaceuticals (Basel) Article MMV’s Malaria Box compound MMV030666 shows multi-stage activity against various strains of Plasmodium falciparum and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed. Physicochemical and pharmacokinetic parameters were determined experimentally (passive permeability) or calculated. Compared to the lead compound a diarylthioether was more active and less cytotoxic resulting in an excellent selectivity index of 850. In addition, pharmacokinetic and physicochemical parameters were improved. MDPI 2022-12-02 /pmc/articles/PMC9783227/ /pubmed/36558954 http://dx.doi.org/10.3390/ph15121503 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hermann, Theresa
Wallner, Robin
Dolensky, Johanna
Seebacher, Werner
Pferschy-Wenzig, Eva-Maria
Kaiser, Marcel
Mäser, Pascal
Weis, Robert
New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title_full New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title_fullStr New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title_full_unstemmed New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title_short New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies
title_sort new derivatives of the multi-stage active malaria box compound mmv030666 and their antiplasmodial potencies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783227/
https://www.ncbi.nlm.nih.gov/pubmed/36558954
http://dx.doi.org/10.3390/ph15121503
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