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Arylmethylamino steroids as antiparasitic agents

Krieg, Reimar and Jortzik, Esther and Goetz, Alice-Anne and Blandin, Stéphanie and Wittlin, Sergio and Elhabiri, Mourad and Rahbari, Mahsa and Nuryyeva, Selbi and Voigt, Kerstin and Dahse, Hans-Martin and Brakhage, Axel and Beckmann, Svenja and Quack, Thomas and Grevelding, Christoph G. and Pinkerton, Anthony B. and Schönecker, Bruno and Burrows, Jeremy and Davioud-Charvet, Elisabeth and Rahlfs, Stefan and Becker, Katja. (2017) Arylmethylamino steroids as antiparasitic agents. Nature communications, 8. p. 14478.

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Official URL: http://edoc.unibas.ch/54659/

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Abstract

In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1-5 nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes. The steroid compounds show low cytotoxicity in mammalian cells and do not induce acute toxicity symptoms in mice. Moreover, 1o has a remarkable activity against the blood-feeding trematode parasite Schistosoma mansoni. The steroid and the hydroxyarylmethylamino moieties are essential for antimalarial activity supporting a chelate-based quinone methide mechanism involving metal or haem bioactivation. This study identifies chemical scaffolds that are rapidly internalized into blood-feeding parasites.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Wittlin, Sergio
Item Type:Article, refereed
Publisher:Nature Publishing Group
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Apr 2017 08:08
Deposited On:25 Apr 2017 09:49

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