From human immunodeficiency virus non-nucleoside reverse transcriptase inhibitors to potent and selective antitrypanosomal compounds

  • Bioorg Med Chem. 2014 Oct 1;22(19):5241-8. doi: 10.1016/j.bmc.2014.08.005.
Muthusamy Venkatraj  1 ,  Kevin K Ariën  2 ,  Jan Heeres  1 ,  Jurgen Joossens  1 ,  Bertrand Dirié  1 ,  Sophie Lyssens  1 ,  Johan Michiels  2 ,  Paul Cos  3 ,  Paul J Lewi  1 ,  Guido Vanham  4 ,  Louis Maes  3 ,  Pieter Van der Veken  1 ,  Koen Augustyns  5
Affiliations
  • 1. Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
  • 2. Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium.
  • 3. Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
  • 4. Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
  • 5. Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. Electronic address: [email protected].
PMID: 25199582 DOI: 10.1016/j.bmc.2014.08.005
Abstract

The presence of a structural recognition motif for the nucleoside P2 transporter in a library of pyrimidine and triazine non-nucleoside HIV-1 Reverse Transcriptase inhibitors, prompted for the evaluation of antitrypanosomal activity. It was demonstrated that the structure-activity relationship for anti-HIV and antitrypanosomal activity was different. Optimization in the diaryl triazine series led to 6-(mesityloxy)-N2-phenyl-1,3,5-triazine-2,4-diamine (69), a compound with potent in vitro and moderate in vivo antitrypanosomal activity.

Keywords
African trypanosomiasis; Antitrypanosomal activity; NNRTIs; Triazines; Trypanosoma brucei.