Suramin: Effectiveness of analogues reveals structural features that are important for the potent trypanocidal activity of the drug

Dietmar Steverding, Ryan A. J. Tinson, Monica Piras, Stephen P. Wren, Stuart A. Rushworth, Mark Searcey, Linda Troeberg

Research output: Contribution to journalArticlepeer-review

Abstract

Suramin was the first effective drug for the treatment of human African sleeping sickness. Structural analogues of the trypanocide have previously been shown to be potent inhibitors of several enzymes. Therefore, four suramin analogues lacking the methyl group on the intermediate rings and with different regiochemistry of the naphthalenetrisulphonic acid groups and the phenyl rings were tested to establish whether they exhibited improved antiproliferative activity against bloodstream forms of Trypanosomes brucei compared to the parent compound. The four analogues exhibited low trypanocidal activity and weak inhibition of the antitrypanosomal activity of suramin in competition experiments. This indicates that the strong trypanocidal activity of suramin is most likely due to the presence of methyl groups on its intermediate rings and to the specific regiochemistry of naphthalenetrisulphonic acid groups. These two structural features are also likely to be important for the inhibition mechanism of suramin because DNA distribution and nucleus/kinetoplast configuration analyses suggest that the analogues inhibit mitosis while suramin inhibits cytokinesis.

Original languageEnglish
Article number108744
Number of pages6
JournalExperimental Parasitology
Volume260
Early online date19 Mar 2024
DOIs
Publication statusE-pub ahead of print - 19 Mar 2024

Keywords

  • Competition assay
  • Flow cytometry
  • Suramin analogues
  • Trypanocidal activity
  • Trypanosoma brucei

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