Convenient synthesis of alternatively bridged tryptophan ketopiperazines and their activities against trypanosomatid parasites

Peter E. Cockram, Callum Turner, Alexandra M. Z. Slawin, Terry Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

There is an urgent need for the development of new treatments against trypanosomatid parasites; the causative agents of some of the most debilitating diseases in the developing world. This work targets an interesting 6-5-6-6 fused carboline scaffold, accessing a range of substituted derivatives through stereospecific intramolecular Pictet-Spengler condensation. Modification of the cyclisation conditions allowed retention of the carbamate protecting group and gave insight into the reaction mechanism. Compounds' bioactivities were measured against T. brucei, T. cruzi, L. major and HeLa cells. We have identified promising pan-trypanocidal lead compounds based on the core scaffold, and highlight key SAR trends which will be useful for the future development of these compounds as potent trypanocidal agents.
Original languageEnglish
Article numbere202100664
Number of pages10
JournalChemMedChem
Volume17
Issue number4
Early online date5 Jan 2022
DOIs
Publication statusPublished - 16 Feb 2022

Keywords

  • Cyclization
  • Polycycles
  • Antiprotazoal agents
  • Biological activity
  • Structure activity relationships

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