Selective accumulation of a novel antimalarial rhodacyanine derivative, SSJ-127, in an organelle of Plasmodium berghei.
SSJ-127, a novel antimalarial rhodacyanine derivative, has shown potent antimalarial activity against chloroquine-resistant Plasmodium strains in vitro and subcutaneous administration of SSJ-127 results in a complete cure of a mouse malaria model. SSJ-127 was detected by fluorescence microscopy in the mouse malaria parasites Plasmodium berghei after exposure of infected red blood cells to the compound in vitro and in vivo. Selective accumulation of SSJ-127 in an organelle is observed in all blood stages of live malaria parasites. The organelle is clearly different from the mitochondrion and the nucleus in terms of morphology. The shape of the organelle changed during the asexual blood stages of the parasite. There was always a close association between the organelle and the mitochondrion. These results raised the possibility that SSJ-127 accumulates in an apicoplast of the malaria parasite and affects protozoan parasite-specific pathways.
Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 143-8501, Japan. m-kawai@hoshi.ac.jp
Mayumi
M
Ikegami-Kawai
Chika
C
Arai
Yuko
Y
Ogawa
Ryohei
R
Yanoshita
Masataka
M
Ihara
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020112:Rhodamine 123 / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000962:Antimalarials; D052160:Benzothiazoles; D010080:Oxazoles; D011726:Pyridinium Compounds; C555999:SSJ 127; D013844:Thiazoles; C481079:rhodacyanine; D020112:Rhodamine 123