Methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species

Beatrice Irungu; Daniel Kiboi; Bernard Langat; Geoffrey Rukunga; Sergio Wittlin; Alexis Nzila

doi:10.1016/j.exppara.2009.06.007

Methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species

Beatrice Irungu, Daniel Kiboi, Bernard Langat, Geoffrey Rukunga, Sergio Wittlin, Alexis Nzila^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.

Original language	English
Pages (from-to)	118-121
Number of pages	4
Journal	Experimental Parasitology
Volume	123
Issue number	2
DOIs	https://doi.org/10.1016/j.exppara.2009.06.007
State	Published - Oct 2009
Externally published	Yes

Bibliographical note

Funding Information:
We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by the European and Developing Countries Clinical Trials Partnership (EDCTP). This work was supported in part by Global Health Research Award GHRA-06-03 from the Health Research Board (Ireland) to Angus Bell and A.N., D.K. and B.L. are Masters Degree students supported by GHRA-06-03.

Keywords

Aminopterin
Antifolate
Folate receptor
Methotrexate
Plasmodium berghei
Plasmodium chabaudi and Plasmodium vinckei
Plasmodium yoelii yoelii
Pyrimethamine

ASJC Scopus subject areas

Parasitology
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.exppara.2009.06.007

Cite this

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title = "Methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species",

abstract = "The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.",

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author = "Beatrice Irungu and Daniel Kiboi and Bernard Langat and Geoffrey Rukunga and Sergio Wittlin and Alexis Nzila",

note = "Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by the European and Developing Countries Clinical Trials Partnership (EDCTP). This work was supported in part by Global Health Research Award GHRA-06-03 from the Health Research Board (Ireland) to Angus Bell and A.N., D.K. and B.L. are Masters Degree students supported by GHRA-06-03.",

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AU - Nzila, Alexis

N1 - Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish these data. This work was supported by the European and Developing Countries Clinical Trials Partnership (EDCTP). This work was supported in part by Global Health Research Award GHRA-06-03 from the Health Research Board (Ireland) to Angus Bell and A.N., D.K. and B.L. are Masters Degree students supported by GHRA-06-03.

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N2 - The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.

AB - The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.

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Methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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