Publication: A mitochondria-penetrating peptide exerts potent anti-plasmodium activity and localizes at parasites’ mitochondria
Issued Date
2021-12-01
Resource Type
ISSN
20796382
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2-s2.0-85121611286
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Mahidol University
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SCOPUS
Bibliographic Citation
Antibiotics. Vol.10, No.12 (2021)
Suggested Citation
Sangdao Somsri, Mathirut Mungthin, Natthaporn Klubthawee, Poom Adisakwattana, Warunee Hanpithakpong, Ratchaneewan Aunpad A mitochondria-penetrating peptide exerts potent anti-plasmodium activity and localizes at parasites’ mitochondria. Antibiotics. Vol.10, No.12 (2021). doi:10.3390/antibiotics10121560 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/75896
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Title
A mitochondria-penetrating peptide exerts potent anti-plasmodium activity and localizes at parasites’ mitochondria
Abstract
Mitochondria are considered a novel drug target as they play a key role in energy produc-tion and programmed cell death of eukaryotic cells. The mitochondria of malaria parasites differ from those of their vertebrate hosts, contributing to the drug selectivity and the development of anti-malarial drugs. (Fx r)3, a mitochondria-penetrating peptide or MPP, entered malaria-infected red cells without disrupting the membrane and subsequently killed the blood stage of P. falciparum parasites. The effects were more potent on the late stages than on the younger stages. Confocal microscopy showed that the (Fx r)3 intensely localized at the parasite mitochondria. (Fx r)3 highly affected both the lab-strain, chloroquine-resistant K1, and freshly isolated malaria parasites. (Fx r)3 (1 ng/mL to 10 µg/mL) was rarely toxic towards various mammalian cells, i.e., mouse fibroblasts (L929), human leukocytes and erythrocytes. At a thousand times higher concentration (100 µg/mL) than that of the antimalarial activity, cytotoxicity and hemolytic activity of (Fx r)3 were observed. Compared with the known antimalarial drug, atovaquone, (Fx r)3 exhibited more rapid killing activity. This is the first report on antimalarial activity of (Fx r)3, showing localization at parasites’ mitochondria.