2. Academic Validation
  3. Synthesis of bicyclic 1,4-thiazepines as novel anti- Trypanosoma brucei brucei agents

Synthesis of bicyclic 1,4-thiazepines as novel anti- Trypanosoma brucei brucei agents

  • Medchemcomm. 2019 Jun 11;10(8):1481-1487. doi: 10.1039/c9md00064j.
Franco Vairoletti 1,  Andrea Medeiros 2 3,  Pablo Fontán 1,  Jennifer Meléndrez 1,  Carlos Tabárez 1,  Gustavo Salinas 4,  Jaime Franco 2,  Marcelo A Comini 2,  Jenny Saldaña 5,  Vojtech Jancik 6,  Graciela Mahler 1,  Cecilia Saiz 1
Affiliations

Affiliations

  • 1 Laboratorio de Química Farmacéutica , Departamento de Química Orgánica , Facultad de Química , Universidad de la República , Montevideo , Uruguay . Email: gmahler@fq.edu.uy ; Email: csaiz@fq.edu.uy.
  • 2 Group Redox Biology of Trypanosomes , Institut Pasteur de Montevideo , Montevideo , Uruguay.
  • 3 Departamento de Bioquímica , Facultad de Medicina , Universidad de la República , Montevideo , Uruguay.
  • 4 Worm Biology Laboratory , Unidad Mixta Institut Pasteur de Montevideo-Facultad de Química , UdelaR , Montevideo , Uruguay.
  • 5 Laboratorio de Experimentación Animal , Depto de Ciencias Farmacéuticas , Facultad de Química , Universidad de la República , Montevideo , Uruguay.
  • 6 Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM , Toluca , Mexico.
PMID: 31673311 DOI: 10.1039/c9md00064j
Abstract

1,4-Thiazepines derivatives are pharmacologically important heterocycles with different applications in medicinal chemistry. In the present work, we describe the preparation of new bicyclic thiazolidinyl-1,4-thiazepines 3 by reaction between azadithiane compounds and Michael acceptors. The reaction scope was explored and the yields were optimized. The activity of the new compounds was evaluated against Nippostrongylus brasiliensis and Caenorhabditis elegans as anthelmintic models and Trypanosoma brucei brucei. The most active compound was 3l, showing an EC50 = 2.8 ± 0.7 μM against T. b. brucei and a selectivity index >71.

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