Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents.

@article{Gnoatto2008PharmacomodulationOT,
  title={Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-\{3-[4-(3-aminopropyl)piperazinyl]propyl\}-3-O-acetylursolamide derivatives as antimalarial agents.},
  author={Simone Cristina Baggio Gnoatto and Sophie Susplugas and Luciana Dalla Vechia and Thais B. Ferreira and Alexandra Dassonville-Klimpt and Karine Rigon Zimmer and Catherine Demailly and Sophie Da Nascimento and Jean Guillon and Philippe Grellier and Hugo Verli and Grace Gosmann and Pascal Sonnet},
  journal={Bioorganic & medicinal chemistry},
  year={2008},
  volume={16 2},
  pages={771-82}
}
A series of new piperazine derivatives of ursolic acid was synthesized and tested against Plasmodium falciparum strains. They were also tested on their cytotoxicity effects upon MRC-5 cells. Seven new piperazinyl analogues showed significant activity in the nanomolar range (IC(50)=78-167nM) against Plasmodium falciparum CQ-resistant strain FcB1. A possible mechanism of interaction implicating binding of these compounds to beta-hematin was supported by in vitro tests. Moreover, the importance of… CONTINUE READING