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

Steverding, Dietmar, Tinson, Ryan A. J., Piras, Monica, Wren, Stephen P., Rushworth, Stuart A., Searcey, Mark ORCID: https://orcid.org/0000-0003-2273-8949 and Troeberg, Linda ORCID: https://orcid.org/0000-0003-0939-4651 (2024) Suramin: Effectiveness of analogues reveals structural features that are important for the potent trypanocidal activity of the drug. Experimental Parasitology, 260. ISSN 0014-4894

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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 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.

Item Type: Article
Additional Information: Funding information: This work was funded in part by Versus Arthritis (grant number 21776).
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: LivePure Connector
Date Deposited: 20 Mar 2024 12:30
Last Modified: 10 Apr 2024 14:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/94728
DOI: 10.1016/j.exppara.2024.108744

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