Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum

Author:

Ngwa CheORCID,Stratmann Rabea,Musabyimana Jean,Pannen Kristina,Schöbel Jan-HendrikORCID,Frings Marcus,Schiffers Ingo,Quaranta CalogeroORCID,Koschmieder SteffenORCID,Chatain NicolasORCID,Pradel GabrieleORCID,Bolm CarstenORCID

Abstract

Malaria is one of the deadliest tropical diseases, especially causing havoc in children under the age of five in Africa. Although the disease is treatable, the rapid development of drug resistant parasites against frontline drugs requires the search for novel antimalarials. In this study, we tested a series of organosulfur compounds from our internal library for their antiplasmodial effect against Plasmodium falciparum asexual and sexual blood stages. Some active compounds were also obtained in enantiomerically pure form and tested individually against asexual blood stages of the parasite to compare their activity. Out of the 23 tested compounds, 7 compounds (1, 2, 5, 9, 15, 16, and 17) exhibited high antimalarial activity, with IC50 values in the range from 2.2 ± 0.64 to 5.2 ± 1.95 µM, while the other compounds showed moderate to very low activity. The most active compounds also exhibited high activity against the chloroquine-resistant strain, reduced gametocyte development and were not toxic to non-infected red blood cells and Hela cells, as well as the hematopoietic HEL cell line at concentrations below 50 µM. To determine if the enantiomers of the active compounds display different antimalarial activity, enantiomers of two of the active compounds were separated and their antimalarial activity compared. The results show a higher activity of the (–) enantiomers as compared to their (+) counterparts. Our combined data indicate that organosulfur compounds could be exploited as antimalarial drugs and enantiomers of the active compounds may represent a good starting point for the design of novel drugs to target malaria.

Funder

Deutsche Forschungsgemeinschaft

RWTH profile area MSE

German Academic Exchange Service

Publisher

MDPI AG

Subject

Infectious Diseases,Public Health, Environmental and Occupational Health,General Immunology and Microbiology

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