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antimalarials

The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis

September 8, 2021 - 17:07 -- Open Access
Author(s): 
Chan XHS, Haeusler IL, White NJ, et al.
Reference: 
PLoS Med. 2021 Sep 7;18(9):e1003766

Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.

NOT Open Access | Ototoxic hearing loss from antimalarials: A systematic narrative review

September 8, 2021 - 17:04 -- NOT Open Access
Author(s): 
Dillard LK, Fullerton AM, McMahon CM
Reference: 
Travel Med Infect Dis. 2021 Sep-Oct;43:102117 Background

Drugs used in curative and prophylactic antimalarial treatment may be ototoxic and lead to permanent hearing loss, but there is no consensus regarding prevalence and permanence of ototoxic hearing loss caused by antimalarials. The purpose of this systematic narrative review was to synthesize current evidence on antimalarial ototoxicity in human populations.

NOT Open Access | Cyclic Tetrapeptide HDAC Inhibitors with Improved Plasmodium falciparum Selectivity and Killing Profile

September 8, 2021 - 16:59 -- NOT Open Access
Author(s): 
Collins JE, Lee JW, Bohmer MJ, Welden JD, Arshadi AK, Du L, Cichewicz RH, Chakrabarti D
Reference: 
ACS Infect Dis. 2021 Sep 7

Cyclic tetrapeptide histone deacetylase inhibitors represent a promising class of antiplasmodial agents that epigenetically disrupt a wide range of cellular processes in Plasmodium falciparum. Unfortunately, certain limitations, including reversible killing effects and host cell toxicity, prevented these inhibitors from further development and clinical use as antimalarials.

Not Open Access | Oral-maxillofacial adverse events related to antimalarials

September 8, 2021 - 16:11 -- NOT Open Access
Author(s): 
Shuai Y, Wang J, Jiang H, Yu Y, Jin L
Reference: 
Oral Dis. 2021 Sep;27(6):1376-1382

Malaria is a worldwide parasitic disease, which affects millions of lives every year. Various medications are recommended by WHO for prevention and treatment of malaria. However, adverse events caused by antimalarials were frequently reported, some of which were severe and fatal.

Knowledge of Antimalarials and Health Seeking Behaviour of Households in Case of Suspected Malaria in Democratic Republic of the Congo

September 1, 2021 - 17:18 -- Open Access
Author(s): 
Ntamabyaliro NY, Burri C, Tona GL, et al.
Reference: 
Trop Med Infect Dis. 2021 Aug 26;6(3):157

The Democratic Republic of the Congo (DRC) is heavily affected by malaria despite availability of effective treatments. Ignorance and unrecommended behaviour toward a suspected malaria case in households may contribute to this problem.

Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials

September 1, 2021 - 15:43 -- Open Access
Author(s): 
Laleu B, Akao Y, Kamaura M, et al.
Reference: 
J Med Chem. 2021 Aug 26

A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies led to identification of a potent inhibitor 19f, 95-fold more potent than the original hit compound, active against laboratory-resistant strains of malaria.

NOT Open Access | Treatment with chloroquine is retinotoxic in captive African penguins (Speniscus demersus). Attenuation and recovery of electroretinographic responses

April 28, 2021 - 14:05 -- NOT Open Access
Author(s): 
Ross M, Avni-Magen N, Pe'er O, Berkowitz A, Ofri R
Reference: 
Vet Ophthalmol. 2021 Apr 26

To evaluate the effect of prophylactic anti‐malarial chloroquine treatment, and its cessation, on electroretinographic (ERG) responses of captive African penguins.

NOT Open Access | Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual-Stage Activity

April 14, 2021 - 08:19 -- NOT Open Access
Author(s): 
Lima MNN, Borba JVB, Andrade CH, et al.
Reference: 
ChemMedChem. 2021 Apr 8;16(7):1093-1103

Increasing reports of multidrug-resistant malaria parasites urge the discovery of new effective drugs with different chemical scaffolds. Protein kinases play a key role in many cellular processes such as signal transduction and cell division, making them interesting targets in many diseases. Protein kinase 7 (PK7) is an orphan kinase from the Plasmodium genus, essential for the sporogonic cycle of these parasites.

NOT Open Access | Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment

January 31, 2021 - 15:53 -- NOT Open Access
Author(s): 
Biosca A, Cabanach P, Abdulkarim M, Gumbleton M, Gómez-Canela C, Ramírez M, Bouzón-Arnáiz I, Avalos-Padilla Y, Borros S, Fernàndez-Busquets X
Reference: 
J Control Release. 2021 Jan 23:S0168-3659(21)00037-7

The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting of Plasmodium falciparum-infected vs. parasite-free red blood cells (74.8%/0.8% respectively), which was maintained upon encapsulation of the lipophilic antimalarial drug curcumin (82.6%/0.3%).

Identification and Assessment of Plasmodium berghei Merozoites and Cell Cycle by Flow Cytometry

January 27, 2021 - 15:36 -- Open Access
Author(s): 
Li Q, Xie LH, Zhang J, Pybus BS
Reference: 
Mil Med. 2021 Jan 25;186(Supplement_1):108-115

The asexual blood stages of the Plasmodium berghei life cycle including merozoites are attractive targets for transmission blocking vaccines and drugs. Improved understanding of P. berghei life cycle stage growth and development would provide new opportunities to evaluate antimalarial vaccines and drugs.

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