100 Years of Suramin

Abstract

Suramin is 100 years old and is still being used to treat the first stage of acute human sleeping sickness, caused by Trypanosoma bruceirhodesiense Suramin is a multifunctional molecule with a wide array of potential applications, from parasitic and viral diseases to cancer, snakebite, and autism. Suramin is also an enigmatic molecule: What are its targets? How does it get into cells in the first place? Here, we provide an overview of the many different candidate targets of suramin and discuss its modes of action and routes of cellular uptake. We reason that, once the polypharmacology of suramin is understood at the molecular level, new, more specific, and less toxic molecules can be identified for the numerous potential applications of suramin.

Keywords: Trypanosoma brucei; human African trypanosomiasis; polypharmacology; sleeping sickness; suramin.

FIG 1

Suramin structure and medicinal chemistry parameters. Except for its good solubility in water, suramin lacks lead-like properties as defined, e.g., by Lipinski’s rule of 5 (186).

FIG 2

Publications on suramin in PubMed. Cumulative numbers are shown for papers on suramin and trypanosomes or trypanosomiasis (search term “trypanosom*”), cancer (“cancer OR tumor”), viruses (“virus OR viral OR hiv OR aids”), and toxins (“toxin OR venom”). Other papers on suramin are also shown. There is no saturation yet, and it is surprising that only a minority of the publications on suramin actually deal with trypanosomes.