title: Antimalarial effect of N-acetyl-L-Leucyl-L-leucyl-L-norleucinal by the inhibition of Plasmodium falciparum Calpain.
abstract: The biological understanding of malaria parasites has increased considerably over the past two decades with the discovery of many potential targets for the development of new antimalarial drugs. Calpain, a cysteine protease of Plasmodium falciparum, is believed to be a central mediator essential for parasitic activity. However, the utility of calpain as a potential anti-malarial target in P. falciparum has not been fully determined. In the present study, we determined the effect of N-acetyl-L-Leucyl-L-leucyl-L-norleucinal (ALLN)-treatment on the expression of calpain in erythrocytic stages of P. falciparum and its usefulness as an antimalarial chemotherapeutic agent. ALLN was shown to have low toxicity to HeLa cells but high toxicity to malaria. ALLN inhibited the expression of calpain in ring, trophozoite and schizont stages when treated for 48 h. Also, after 48 h, samples were characterized by 6.15% and 0% parasitemia without ALLN treatment and with ALLN treatment, respectively. Brightfield and confocal microscopy revealed that ALLN treatment affects merozoite maturation. As ALLN concentration increased from 1 muM to 100 microM, ring stage parasites did not mature into the schizont stage. When ALLN treatment was continued for 48 h, it also significantly inhibited the maturation of ring-stage parasites into trophozoite or schizont stages and survival of malarial parasites. Taken together, these findings suggest that ALLN inhibit the maturation and survival of P. falciparum and calpain expression, and thus has potential utility as an antimalarial chemotherapeutic agent.
authors: Department of Infection Biology, Zoonosis Research Center, School of Medicine, Wonkwang University, Iksan 570-749, Korea.
authors: Suk-Yul
authors: SY
authors: Jung
authors: Bing
authors: B
authors: Zheng
authors: Yun-Young
authors: YY
authors: Choi
authors: Byoung Yul
authors: BY
authors: Soh
authors: Sung Yeon
authors: SY
authors: Kim
authors: Kie-In
authors: KI
authors: Park
authors: Hyun
authors: H
authors: Park
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D018512:Parasitemia / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D052939:Schizonts / Q000187:drug effects; D053058:Trophozoites / Q000187:drug effects
chemical_list: D000962:Antimalarials; D007976:Leupeptins; D015800:Protozoan Proteins; C063261:acetylleucyl-leucyl-norleucinal; D002154:Calpain