TY - JOUR
T1 - Stage specific activity of synthetic antimalarial endoperoxides, N-89 and N-251, against Plasmodium falciparum
AU - Morita, Masayuki
AU - Koyama, Takahiko
AU - Sanai, Hitomi
AU - Sato, Akira
AU - Hiramoto, Akiko
AU - Masuyama, Araki
AU - Nojima, Masatomo
AU - Wataya, Yusuke
AU - Kim, Hye Sook
N1 - Funding Information:
We thank Dr. Hikoya Hayatsu (Okayama University) for helpful discussions. This study was partially supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) (Project No. 04-09 and 09-21 , PI; Y.W.), Grant-in-Aid for Scientific Research (B) ( 25305008 , H.-S.K.), and Grant-in-Aid for Scientific Research (C) ( 22590099 , H.-S.K.) from the Ministry of Education, Culture, Sports, Science and Technologies, Japan , and Drug Discovery Project for Intractable Infectious Diseases of Okayama University (IIDPO) (2010).
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - We have reported that two endoperoxides, N-89 and N-251, synthesized in 2001, possess potent antimalarial activities. Aiming at their eventual use for curing malaria in humans, we have been investigating various aspects of their antimalarial actions. Here we show that N-89 and N-251 inhibit the growth of Plasmodium falciparum within human erythrocytes in vitro at its lifecycle stage 'trophozoite' specifically. It is known that artemisinin compounds, which are currently used for curing malaria, have other stage-specificities. Therefore, it is likely that the antimalarial mechanism of N-89 and N-251 differs from those of artemisinin compounds. As malaria parasites resistant to artemisinin-based combination therapy are currently emerging in some tropical regions, N-89 and N-251 are candidates for overcoming these new problems.
AB - We have reported that two endoperoxides, N-89 and N-251, synthesized in 2001, possess potent antimalarial activities. Aiming at their eventual use for curing malaria in humans, we have been investigating various aspects of their antimalarial actions. Here we show that N-89 and N-251 inhibit the growth of Plasmodium falciparum within human erythrocytes in vitro at its lifecycle stage 'trophozoite' specifically. It is known that artemisinin compounds, which are currently used for curing malaria, have other stage-specificities. Therefore, it is likely that the antimalarial mechanism of N-89 and N-251 differs from those of artemisinin compounds. As malaria parasites resistant to artemisinin-based combination therapy are currently emerging in some tropical regions, N-89 and N-251 are candidates for overcoming these new problems.
KW - Antimalarial candidates
KW - N-251
KW - N-89
KW - Stage-specificity
KW - Synthetic endoperoxides
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U2 - 10.1016/j.parint.2014.10.007
DO - 10.1016/j.parint.2014.10.007
M3 - Article
C2 - 25449979
AN - SCOPUS:84910653880
VL - 64
SP - 113
EP - 117
JO - Parasitology International
JF - Parasitology International
SN - 1383-5769
IS - 1
ER -
