Deceiving and escaping complement – the evasive journey of the malaria parasite

Inklaar, Maartje; Barillas‐Mury, Carolina; Jore, Matthijs M.

doi:10.1016/j.pt.2022.08.013

Cited by 3 publications

(4 citation statements)

References 97 publications

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“…We have reported on four new AQ metal complexes, [Ru-(Cl) 2 (AQ)(η 6 -p-cymene)] (1), [Ru(AQ)(η 6 -p-cymene)(2,2'-bipyridine)](PF 6 ) 2 (2), [Ru(Cl)(AQ)(η 6 -p-cymene)(PPh 3 )]PF 6 (3) and [Au-(AQ)(PPh 3 )]PF 6 (4), and fully characterized them by analytical and spectral methods (elemental analysis, UV-vis, FTIR, con-ductivity, mass spectrometry, and NMR). Our analyses indicate that the AQ ligand binds to the metal center through the nitrogen from the quinoline motif.…”

Section: Discussionmentioning

confidence: 99%

“…This step is performed in order to release its nitrogen atoms for metal coordination. To stabilize the cationic species, PF 6 (4) were yellowish or brownish in color. These solids were stable when exposed to light and air, and they were insoluble in water, hexane, and diethyl ether, but soluble in methanol, acetone (except for complex 1), DMSO, dichloromethane, acetonitrile, and chloroform.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

“…Some of the infected blood cells stop reproducing asexually and transform into gametocytes, which are the sexual forms of the parasite that circulate in the bloodstream, rather than replicating. When a mosquito bites an infected person, it consumes gametocytes, which later mature into sporozoites and restart the life cycle [4] …”

Section: Introductionmentioning

confidence: 99%

“…When a mosquito bites an infected person, it consumes gametocytes, which later mature into sporozoites and restart the life cycle. [4] The main symptoms of uncomplicated malaria are fever, sweating, chills, headache, fatigue, diarrhea, nausea, and breathing problems. It can progress to cause severe anemia or the most complicated form of malaria (cerebral malaria).…”

Section: Introductionmentioning

confidence: 99%

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Antimalarial Agents Derived from Metal‐Amodiaquine Complexes with Activity in Multiple Stages of the Plasmodium Life Cycle

Colina‐Vegas

Silva²,

Pereira

et al. 2023

Chemistry A European J

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Quinolines are excellent ligands for metal coordination and are deployed as drugs for malaria treatment. There is a growing body of evidence indicating that metal complexes can be conjugated with antimalarial quinolines to be used as chemical tools to overcome the disadvantages of quinolines, improving their bioactive speciation, cellular distribution, and subsequently broadening the spectrum of activity to multiple stages of the complex Plasmodium life cycle. In this study, four novel complexes of ruthenium(II) and gold(I) containing amodiaquine (AQ) were synthesized and a careful chemical characterization revealed the precise coordination site of AQ to the metals. Their speciation in solution was investigated, demonstrating the stability of the quinoline‐metal bond. Ru(II)‐ and Au(I)‐AQ complexes were demonstrated to be potent and efficacious in inhibiting parasite growth in multiple stages of the Plasmodium life cycle assayed in vitro and in vivo. These properties could be attributed to the ability of the metal‐AQ complexes to reproduce the suppression of heme detoxification induced by AQ, while also inhibiting other processes in the parasite life cycle, which can be attributed to the action of the metallic species. These findings indicate that metal coordination is a potential chemical tool for drug design and discovery in malaria.

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Section: Discussionmentioning

confidence: 99%

Section: Synthesis and Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antimalarial Agents Derived from Metal‐Amodiaquine Complexes with Activity in Multiple Stages of the Plasmodium Life Cycle

Colina‐Vegas

Silva²,

Pereira

et al. 2023

Chemistry A European J

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Conserved proteins of Eimeria and their applications to develop universal subunit vaccine against chicken coccidiosis

Xu,

2024

Veterinary Vaccine

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Novel systems to study vector-pathogen interactions in malaria

Parres-Mercader

Pance

Gómez-Díaz

2023

Front. Cell. Infect. Microbiol.

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Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating “de novo” genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.

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Deceiving and escaping complement – the evasive journey of the malaria parasite

Cited by 3 publications

References 97 publications

Antimalarial Agents Derived from Metal‐Amodiaquine Complexes with Activity in Multiple Stages of the Plasmodium Life Cycle

Antimalarial Agents Derived from Metal‐Amodiaquine Complexes with Activity in Multiple Stages of the Plasmodium Life Cycle

Conserved proteins of Eimeria and their applications to develop universal subunit vaccine against chicken coccidiosis

Novel systems to study vector-pathogen interactions in malaria

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