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

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...

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Autores principales: Ngwa, Che Julius, Stratmann, Rabea, Musabyimana, Jean Pierre, Pannen, Kristina, Schöbel, Jan-Hendrik, Frings, Marcus, Schiffers, Ingo, Quaranta, Calogero, Koschmieder, Steffen, Chatain, Nicolas, Pradel, Gabriele, Bolm, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785921/
https://www.ncbi.nlm.nih.gov/pubmed/36548671
http://dx.doi.org/10.3390/tropicalmed7120416
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author Ngwa, Che Julius
Stratmann, Rabea
Musabyimana, Jean Pierre
Pannen, Kristina
Schöbel, Jan-Hendrik
Frings, Marcus
Schiffers, Ingo
Quaranta, Calogero
Koschmieder, Steffen
Chatain, Nicolas
Pradel, Gabriele
Bolm, Carsten
author_facet Ngwa, Che Julius
Stratmann, Rabea
Musabyimana, Jean Pierre
Pannen, Kristina
Schöbel, Jan-Hendrik
Frings, Marcus
Schiffers, Ingo
Quaranta, Calogero
Koschmieder, Steffen
Chatain, Nicolas
Pradel, Gabriele
Bolm, Carsten
author_sort Ngwa, Che Julius
collection PubMed
description 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 IC(50) 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.
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spelling pubmed-97859212022-12-24 Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum Ngwa, Che Julius Stratmann, Rabea Musabyimana, Jean Pierre Pannen, Kristina Schöbel, Jan-Hendrik Frings, Marcus Schiffers, Ingo Quaranta, Calogero Koschmieder, Steffen Chatain, Nicolas Pradel, Gabriele Bolm, Carsten Trop Med Infect Dis Article 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 IC(50) 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. MDPI 2022-12-03 /pmc/articles/PMC9785921/ /pubmed/36548671 http://dx.doi.org/10.3390/tropicalmed7120416 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ngwa, Che Julius
Stratmann, Rabea
Musabyimana, Jean Pierre
Pannen, Kristina
Schöbel, Jan-Hendrik
Frings, Marcus
Schiffers, Ingo
Quaranta, Calogero
Koschmieder, Steffen
Chatain, Nicolas
Pradel, Gabriele
Bolm, Carsten
Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title_full Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title_fullStr Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title_full_unstemmed Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title_short Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite Plasmodium falciparum
title_sort evaluation of chiral organosulfur compounds on their activity against the malaria parasite plasmodium falciparum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785921/
https://www.ncbi.nlm.nih.gov/pubmed/36548671
http://dx.doi.org/10.3390/tropicalmed7120416
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