Back to Search Start Over

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

Authors :
Theresa Hermann
Robin Wallner
Johanna Dolensky
Werner Seebacher
Eva-Maria Pferschy-Wenzig
Marcel Kaiser
Pascal Mäser
Robert Weis
Source :
Pharmaceuticals, Vol 15, Iss 12, p 1503 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14248247
Volume :
15
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.603281af140647b39bfc9baab0679f20
Document Type :
article
Full Text :
https://doi.org/10.3390/ph15121503