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antimalarial drugs

NOT Open Access | Covalent inhibition of P. falciparum ferredoxin-NADP(+) reductase: Exploring alternative strategies for the development of new antimalarial drugs

November 9, 2021 - 09:10 -- NOT Open Access
Author(s): 
de Rosa M, Nonnis S, Aliverti A
Reference: 
Biochem Biophys Res Commun. 2021 Nov 5;577:89-94

The protozoan Plasmodium falciparum is the main aetiological agent of tropical malaria. Characteristic of the phylum is the presence of a plastid-like organelle which hosts several homologs of plant proteins, including a ferredoxin (PfFd) and its NADPH-dependent reductase (PfFNR). The PfFNR/PfFd redox system is essential for the parasite, while mammals share no homologous proteins, making the enzyme an attractive target for novel and much needed antimalarial drugs.

Intensive surveillance, rapid response and border collaboration for malaria elimination: China Yunnan’s ‘‘3 + 1’’strategy

October 23, 2021 - 18:31 -- Open Access
Author(s): 
Jian-Wei Xu, Zu-Rui Lin, Hong-Ning Zhou, et al.
Reference: 
Malaria Journal 2021 20:396, 9 October 2021

Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission.

NOT Open Access | Determination of antimalarial drugs in pharmaceutical formulations and human blood by liquid chromatography: a review

October 12, 2021 - 10:53 -- NOT Open Access
Author(s): 
Penna EA, de Souza JCQ, de Oliveira MAL, Chellini PR
Reference: 
Anal Methods. 2021 Oct 6

Malaria is a life-threatening disease being treated by oral medication. This is the best treatment to reduce morbidity and mortality, prevent disease progression to the most severe form, lower the transmission of the disease and hinder the appearance of strains resistant to antimalarials.

Not Open Access | High-Content Phenotypic Screen of a Focused TCAMS Drug Library Identifies Novel Disruptors of the Malaria Parasite Calcium Dynamics

October 12, 2021 - 10:04 -- NOT Open Access
Author(s): 
Chia W, Gomez-Lorenzo MG, Tan KSW, et al.
Reference: 
ACS Chem Biol. 2021 Oct 5

The search for new antimalarial drugs with unexplored mechanisms of action is currently one of the main objectives to combat the resistance already in the clinic. New drugs should target specific mechanisms that once initiated lead inevitably to the parasite's death and clearance and cause minimal toxicity to the host. One such new mode of action recently characterized is to target the parasite's calcium dynamics. Disruption of the calcium homeostasis is associated with compromised digestive vacuole membrane integrity and release of its contents, leading to programmed cell death-like features characterized by loss of mitochondrial membrane potential and DNA degradation.

Artemisinin susceptibility in the malaria parasite Plasmodium falciparum: propellers, adaptor proteins and the need for cellular healing

May 12, 2021 - 12:39 -- Open Access
Author(s): 
Sutherland CJ, Henrici RC, Artavanis-Tsakonas K
Reference: 
FEMS Microbiol Rev. 2021 May 5;45(3):fuaa056

Studies of the susceptibility of Plasmodium falciparum to the artemisinin family of antimalarial drugs provide a complex picture of partial resistance (tolerance) associated with increased parasite survival in vitro and in vivo.

The integrity and stability of specimens under different storage conditions for glucose-6-phosphate dehydrogenase deficiency screening using WST-8

May 5, 2021 - 08:56 -- Open Access
Author(s): 
Chamchoy K, Praoparotai A, Pakparnich P, Sudsumrit S, Swangsri T, Chamnanchanunt S, Songdej D, Imwong M, Boonyuen U
Reference: 
Acta Trop. 2021 May;217:105864

Accurate measurement of glucose-6-phosphate dehydrogenase (G6PD) activity is critical for malaria treatment as misclassification of G6PD deficiency could cause serious harm to patients. G6PD activity should be assessed in blood samples on the day of collection. Otherwise, specimens should be stored under suitable conditions to prevent loss of G6PD activity.

NOT Open Access | Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites

April 13, 2021 - 13:26 -- NOT Open Access
Author(s): 
Babbar P, Das P, Manickam Y, Mankad Y, Yadav S, Parvez S, Sharma A, Reddy DS
Reference: 
ACS Infect Dis. 2021 Apr 12

Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics.

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

April 13, 2021 - 13:07 -- Open Access
Author(s): 
Tavella TA, da Silva NSM, Maranhão Costa FT, et al.
Reference: 
ACS Infect Dis. 2021 Apr 9;7(4):759-776

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities.

Hydroxychloroquine Controversies: Clinical Trials, Epistemology, and the Democratization of Science

November 19, 2020 - 13:23 -- Open Access
Author(s): 
Berlivet L, Löwy I
Reference: 
Med Anthropol Q. 2020 Nov 18

The claim that anti-malaria drugs, chloroquine and hydroxychloroquine, can cure COVID-19 became a focus of fierce political battles that pitted promoters of these pharmaceuticals, Presidents Bolsonaro and Trump among them, against "medical elites." At the center of these battles are different meanings of effectiveness in medicine, the complex role of randomized clinical trials (RCTs) in proving such effectiveness, the task of medical experts and the state in regulating pharmaceuticals, patients' activism, and the collective production of medical knowledge.

Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor

November 19, 2020 - 13:15 -- Open Access
Author(s): 
Zhou J, Huang Z, Zheng L, Hei Z, Wang Z, Yu B, Jiang L, Wang J, Fang P
Reference: 
Nucleic Acids Res. 2020 Nov 18;48(20):11566-11576

Aminoacyl-tRNA synthetases are attractive targets for the development of antibacterial, antifungal, antiparasitic agents and for the treatment of other human diseases. Lysyl-tRNA synthetase (LysRS) from this family has been validated as a promising target for the development of antimalarial drugs. Here, we developed a high-throughput compatible assay and screened 1215 bioactive compounds to identify Plasmodium falciparum cytoplasmic LysRS (PfLysRS) inhibitor.

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