Proteomic analysis of Plasmodium falciparum response to isocryptolepine derivative

PloS One
Kitiya RujimongkonOnrapak Reamtong

Abstract

Drug-resistant strains of malaria parasites have emerged for most of antimalarial medications. A new chemotherapeutic compound is needed for malarial therapy. Antimalarial activity against both drug-sensitive and drug-resistant P. falciparum has been reported for an isocryptolepine derivative, 8-bromo-2-fluoro-5-methyl-5H-indolo[3,2-c]quinoline (ICL-M), which also showed less toxicity to human cells. ICL-M has indoloquinoline as a core structure and its mode of action remains unclear. Here, we explored the mechanisms of ICL-M in P. falciparum by assessing the stage-specific activity, time-dependent effect, a proteomic analysis and morphology. Since human topo II activity inhibition has been reported as a function of isocryptolepine derivatives, malarial topo II activity inhibition of ICL-M was also examined in this study. The ICL-M exhibited antimalarial activity against both the ring and trophozoite stages of P. falciparum. Our proteomics analysis revealed that a total of 112 P. falciparum proteins were differentially expressed after ICL-M exposure; among these, 58 and 54 proteins were upregulated and downregulated, respectively. Proteins localized in the food vacuole, nucleus, and cytoplasm showed quantitative alterations aft...Continue Reading

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Citations

Aug 9, 2020·Genes·Janaina Macedo-da-SilvaLivia Rosa-Fernandes
Oct 8, 2020·Biomolecules·Maryia Karpiyevich, Katerina Artavanis-Tsakonas
Jun 29, 2021·Frontiers in Cellular and Infection Microbiology·Daffiny Sumam de OliveiraEdmarcia Elisa de Souza
Oct 6, 2021·ChemMedChem·Warabhorn RodphonSomsak Ruchirawat

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Methods Mentioned

BETA
electrophoresis
Assay
protein folding
sumoylation
electron microscopy

Software Mentioned

STRING
mascot
GRAFIT
DataAnalysis
STRINGS
Mascot daemon

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