2. Academic Validation
  3. From human immunodeficiency virus non-nucleoside reverse transcriptase inhibitors to potent and selective antitrypanosomal compounds

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

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: Koen.Augustyns@uantwerpen.be.
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.

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