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

Autor: Steverding D; Bob Champion Research and Education Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. Electronic address: d.steverding@uea.ac.uk., Tinson RAJ; Bob Champion Research and Education Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; School of Pharmacy, University of East Anglia, Norwich, United Kingdom., Piras M; Target Discovery Institute, University of Oxford, Oxford, United Kingdom., Wren SP; Department of Chemical and Pharmaceutical Sciences, Kingston University London, Kingston Upon Thames, United Kingdom., Rushworth SA; Bob Champion Research and Education Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom., Searcey M; School of Pharmacy, University of East Anglia, Norwich, United Kingdom., Troeberg L; Bob Champion Research and Education Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Jazyk: angličtina
Zdroj: Experimental parasitology [Exp Parasitol] 2024 May; Vol. 260, pp. 108744. Date of Electronic Publication: 2024 Mar 19.
DOI: 10.1016/j.exppara.2024.108744
Abstrakt: 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.
Competing Interests: Declaration of competing interest All authors declare that there were no commercial or financial interests or any other conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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