Synthesis and biological evaluation of CTP synthetase inhibitors as potential agents for the treatment of African trypanosomiasis

Lucia Tamborini, Andrea Pinto, Terry K. Smith, Louise L. Major, Maria C. Iannuzzi, Sandro Cosconati, Luciana Marinelli, Ettore Novellino, Leonardo Lo Presti, Pui E. Wong, Michael P. Barrett, Carlo De Micheli, Paola Conti

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing molecular complexity, by inserting groups able to establish additional interactions with the binding pocket of the enzyme. This strategy has been pursued with the synthesis of a-amino-substituted analogues of Acivicin and N1-substituted pyrazoline derivatives. In general, there is direct correlation between the enzymatic activity and the in vitro anti-trypanosomal efficacy of the derivatives studied here. However, this cannot be taken as a general rule, as other important factors may play a role, notably the ability of uptake/diffusion of the molecules into the trypanosomes.

Original languageEnglish
Pages (from-to)1623-1634
Number of pages12
JournalChemMedChem
Volume7
Issue number9
DOIs
Publication statusPublished - Sept 2012

Keywords

  • Carbon-Nitrogen Ligases
  • Enzyme Inhibitors
  • HeLa Cells
  • Humans
  • Isoxazoles
  • Molecular Docking Simulation
  • Pyrazoles
  • Trypanocidal Agents
  • Trypanosoma brucei brucei
  • Trypanosomiasis, African

Fingerprint

Dive into the research topics of 'Synthesis and biological evaluation of CTP synthetase inhibitors as potential agents for the treatment of African trypanosomiasis'. Together they form a unique fingerprint.

Cite this