biostudies-literatureUnknown15(12)Hermann TMMV's Malaria Box compound MMV030666 shows multi-stage activity against various strains of <i>Plasmodium falciparum</i> 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.Pharmaceuticals (Basel, Switzerland)1503https://www.ebi.ac.uk/biostudies/studies/S-EPMC9783227biostudies-literatureNew Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies.PMC9783227Maser PHermann TPferschy-Wenzig EMSeebacher WWeis RWallner RDolensky JKaiser MfalseNew 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 <i>Plasmodium falciparum</i> 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.2022-01-01T00:00:00Z2022 Dec2025-04-18T15:59:45.735Z2025-04-07T02:53:28.191ZS-EPMC97832273655895410.3390/ph15121503