Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs
Abstract Background The erythrocytic stage of Plasmodium falciparum parasites in humans is clinically important, as the parasites at this growth stage causes malarial symptoms. Most of the currently available anti-malarial drugs target this stage, but the emergence and spread of parasites resistant...
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ftdoajarticles:oai:doaj.org/article:97dba30481ac466fbf546c3cb173afd3 2023-05-15T15:18:04+02:00 Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs Takahiro Tougan Yuji Toya Kinya Uchihashi Toshihiro Horii 2019-01-01T00:00:00Z https://doi.org/10.1186/s12936-019-2642-0 https://doaj.org/article/97dba30481ac466fbf546c3cb173afd3 EN eng BMC http://link.springer.com/article/10.1186/s12936-019-2642-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2642-0 1475-2875 https://doaj.org/article/97dba30481ac466fbf546c3cb173afd3 Malaria Journal, Vol 18, Iss 1, Pp 1-12 (2019) XN-30 analyzer Plasmodium falciparum Erythrocytic stage Anti-malarial drug In vitro drug screening Medicines for Malaria Venture Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2019 ftdoajarticles https://doi.org/10.1186/s12936-019-2642-0 2022-12-31T14:41:56Z Abstract Background The erythrocytic stage of Plasmodium falciparum parasites in humans is clinically important, as the parasites at this growth stage causes malarial symptoms. Most of the currently available anti-malarial drugs target this stage, but the emergence and spread of parasites resistant to anti-malarial drugs are a major challenge to global eradication efforts; therefore, the development of novel medicines is urgently required. In this study, the in vitro anti-malarial activity of five current anti-malarial drugs (artemisinin, atovaquone, chloroquine, mefloquine, and pyrimethamine) and 400 compounds from the Pathogen Box provided by the Medicines for Malaria Venture on P. falciparum parasites was characterized using the XN-30 analyzer. Furthermore, the outcomes obtained using the analyser were classified according to the parasitaemias of total and each developmental stages. Results The growth inhibition rate and the half-maximal (50%) inhibitory concentration (IC50) of the five current anti-malarial drugs were calculated from the parasitaemia detected using the XN-30 analyzer. Respective strains and drugs presented strongly fitted sigmoidal curves, and the median SD at all tested concentrations was 1.6, suggesting that the variation in values measured with the analyser was acceptably low for the comparison of drug efficacy. Furthermore, the anti-malarial activity of the 400 compounds from the Pathogen Box was tested, and 141 drugs were found to be effective. In addition, the efficacy was classified into 4 types (Type I, parasites were arrested or killed without DNA replication; Type II, parasites were arrested or killed similar to Type I, and the parasitaemia was apparently decreased; Type III, parasites progressed to trophozoite without sufficient DNA replication; and Type IV, parasites were arrested at late trophozoite or schizont after DNA replication). Conclusion The current study demonstrates that the XN-30 analyzer objectively, reproducibly, and easily evaluated and characterized the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 18 1 |
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XN-30 analyzer Plasmodium falciparum Erythrocytic stage Anti-malarial drug In vitro drug screening Medicines for Malaria Venture Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
XN-30 analyzer Plasmodium falciparum Erythrocytic stage Anti-malarial drug In vitro drug screening Medicines for Malaria Venture Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Takahiro Tougan Yuji Toya Kinya Uchihashi Toshihiro Horii Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
topic_facet |
XN-30 analyzer Plasmodium falciparum Erythrocytic stage Anti-malarial drug In vitro drug screening Medicines for Malaria Venture Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The erythrocytic stage of Plasmodium falciparum parasites in humans is clinically important, as the parasites at this growth stage causes malarial symptoms. Most of the currently available anti-malarial drugs target this stage, but the emergence and spread of parasites resistant to anti-malarial drugs are a major challenge to global eradication efforts; therefore, the development of novel medicines is urgently required. In this study, the in vitro anti-malarial activity of five current anti-malarial drugs (artemisinin, atovaquone, chloroquine, mefloquine, and pyrimethamine) and 400 compounds from the Pathogen Box provided by the Medicines for Malaria Venture on P. falciparum parasites was characterized using the XN-30 analyzer. Furthermore, the outcomes obtained using the analyser were classified according to the parasitaemias of total and each developmental stages. Results The growth inhibition rate and the half-maximal (50%) inhibitory concentration (IC50) of the five current anti-malarial drugs were calculated from the parasitaemia detected using the XN-30 analyzer. Respective strains and drugs presented strongly fitted sigmoidal curves, and the median SD at all tested concentrations was 1.6, suggesting that the variation in values measured with the analyser was acceptably low for the comparison of drug efficacy. Furthermore, the anti-malarial activity of the 400 compounds from the Pathogen Box was tested, and 141 drugs were found to be effective. In addition, the efficacy was classified into 4 types (Type I, parasites were arrested or killed without DNA replication; Type II, parasites were arrested or killed similar to Type I, and the parasitaemia was apparently decreased; Type III, parasites progressed to trophozoite without sufficient DNA replication; and Type IV, parasites were arrested at late trophozoite or schizont after DNA replication). Conclusion The current study demonstrates that the XN-30 analyzer objectively, reproducibly, and easily evaluated and characterized the ... |
format |
Article in Journal/Newspaper |
author |
Takahiro Tougan Yuji Toya Kinya Uchihashi Toshihiro Horii |
author_facet |
Takahiro Tougan Yuji Toya Kinya Uchihashi Toshihiro Horii |
author_sort |
Takahiro Tougan |
title |
Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
title_short |
Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
title_full |
Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
title_fullStr |
Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
title_full_unstemmed |
Application of the automated haematology analyzer XN-30 for discovery and development of anti-malarial drugs |
title_sort |
application of the automated haematology analyzer xn-30 for discovery and development of anti-malarial drugs |
publisher |
BMC |
publishDate |
2019 |
url |
https://doi.org/10.1186/s12936-019-2642-0 https://doaj.org/article/97dba30481ac466fbf546c3cb173afd3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 18, Iss 1, Pp 1-12 (2019) |
op_relation |
http://link.springer.com/article/10.1186/s12936-019-2642-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2642-0 1475-2875 https://doaj.org/article/97dba30481ac466fbf546c3cb173afd3 |
op_doi |
https://doi.org/10.1186/s12936-019-2642-0 |
container_title |
Malaria Journal |
container_volume |
18 |
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1 |
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1766348305983340544 |