Journal article

Publication year: 2017

Pages: 14478-

Journal: Nature Communications

Volume number: 8

ISSN: 2041-1723

eISSN: 2041-1723

Open access status: Gold

DOI Link: https://doi.org/10.1038/ncomms14478

Publisher: Nature Research

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.

Harvard Citation style: Krieg, R., Jortzik, E., Goetz, A., Blandin, S., Wittlin, S., Elhabiri, M., et al. (2017) Arylmethylamino steroids as antiparasitic agents, Nature Communications, 8, p. 14478. https://doi.org/10.1038/ncomms14478

APA Citation style: Krieg, R., Jortzik, E., Goetz, A., Blandin, S., Wittlin, S., Elhabiri, M., Rahbari, M., Nuryyeva, S., Voigt, K., Dahse, H., Brakhage, A., Beckmann, S., Quack, T., Grevelding, C., Pinkerton, A., Schönecker, B., Burrows, J., Davioud-Charvet, E., Rahlfs, S., ...Becker, K. (2017). Arylmethylamino steroids as antiparasitic agents. Nature Communications. 8, 14478. https://doi.org/10.1038/ncomms14478