Pharmaceuticals (Dec 2022)

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

  • Theresa Hermann,
  • Robin Wallner,
  • Johanna Dolensky,
  • Werner Seebacher,
  • Eva-Maria Pferschy-Wenzig,
  • Marcel Kaiser,
  • Pascal Mäser,
  • Robert Weis

DOI
https://doi.org/10.3390/ph15121503
Journal volume & issue
Vol. 15, no. 12
p. 1503

Abstract

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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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