Activity of Aromathecins against African Trypanosomes

Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00786-18. doi: 10.1128/AAC.00786-18. Print 2018 Nov.

Abstract

African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.

Keywords: Trypanosoma brucei; aromathecin; sleeping sickness; structure-activity; topoisomerase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiprotozoal Agents / therapeutic use*
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • Structure-Activity Relationship
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma / drug effects*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosomiasis, African / drug therapy*
  • Trypanosomiasis, African / parasitology

Substances

  • Antiprotozoal Agents
  • Heterocyclic Compounds, 4 or More Rings
  • Trypanocidal Agents
  • rosettacin