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antimalarial drugs

NOT Open Access | Updated pharmacokinetic considerations for the use of antimalarial drugs in pregnant women

August 3, 2020 - 15:37 -- NOT Open Access
Author(s): 
Moore BR, Davis TME
Reference: 
Expert Opin Drug Metab Toxicol. 2020 Jul 30

The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or treatment of malaria in pregnancy can result in negative maternal/infant outcomes, along with the potential to select for parasite drug resistance, it is imperative that reliable pregnancy-specific dosing recommendations are established.

Hydroxychloroquine in rheumatic autoimmune disorders and beyond

July 28, 2020 - 14:03 -- Open Access
Author(s): 
Nirk EL, Reggiori F, Mauthe M
Reference: 
EMBO Mol Med. 2020 Jul 26:e12476q

Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis.

Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study

July 20, 2020 - 15:55 -- Open Access
Author(s): 
Imwong M, Dhorda M, White NJ, et al.
Reference: 
Lancet Infect Dis. 2020 Jul 14:S1473-3099(20)30228-0

The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018.

Polymorphisms of pfcrt, pfmdr1, and K13-propeller genes in imported falciparum malaria isolates from Africa in Guizhou province, China

July 20, 2020 - 15:28 -- Open Access
Author(s): 
She D, Wang Z, Liang Q, Lu L, Huang Y, Zhang K, An D, Wu J
Reference: 
BMC Infect Dis. 2020 Jul 16;20(1):513

Imported falciparum malaria from Africa has become a key public health challenge in Guizhou Province since 2012. Understanding the polymorphisms of molecular markers of drug resistance can guide selection of antimalarial drugs for the treatment of malaria. This study was aimed to analyze the polymorphisms of pfcrt, pfmdr1, and K13-propeller among imported falciparum malaria cases in Guizhou Province, China.

NOT Open Access | A Chemically Stable Fluorescent Mimic of Dihydroartemisinin, Artemether, and Arteether with Conserved Bioactivity and Specificity Shows High Pharmacological Relevance to the Antimalarial Drugs

July 20, 2020 - 14:52 -- NOT Open Access
Author(s): 
Sissoko A, Vásquez-Ocmín P, Duval R, et al.
Reference: 
ACS Infect Dis. 2020 Jul 10; 6(7):1532-1547

Three novel tracers designed as fluorescent surrogates of artemisinin-derived antimalarial drugs (i.e., dihydroartemisinin, artemether, arteether, and artemisone) were synthesized from dihydroartemisinin.

NOT Open Access | Computational chemogenomics drug repositioning strategy enables the discovery of Epirubicin as a new repurposed hit for P. falciparum and P. vivax

June 30, 2020 - 14:57 -- NOT Open Access
Author(s): 
Ferreira LT, Rodrigues J, Costa FTM, et al.
Reference: 
Antimicrob Agents Chemother. 2020 Jun 29:AAC.02041-19

Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks and time-to-market. Herein we have used this strategy to identify novel antimalarial hits. We performed a comparative in silico chemogenomics approach to select Plasmodium falciparum and P. vivax proteins as potential drug targets and analyzed these using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation.

NOT Open Access | 'Artemisinin Resistance': Something New or Old? Something of a Misnomer

June 29, 2020 - 16:18 -- NOT Open Access
Author(s): 
Wellems TE, Sá JM, Su XZ, Connelly SV, Ellis AC
Reference: 
Trends Parasitol. 2020 Jun 22:S1471-4922(20)30158-6

Artemisinin and its derivatives (ART) are crucial first-line antimalarial drugs that rapidly clear parasitemia, but recrudescences of the infection frequently follow ART monotherapy. For this reason, ART must be used in combination with one or more partner drugs that ensure complete cure.

NOT Open Access | Heterologous Expression, Purification, and Functional Analysis of the Plasmodium falciparum Phosphatidylinositol 4-Kinase IIIß

June 17, 2020 - 12:59 -- NOT Open Access
Author(s): 
Sternberg AR, Roepe PD
Reference: 
Biochemistry. 2020 Jun 16

Recently we heterologously expressed, purified, and analyzed the function of the sole Plasmodium falciparum phosphatidylinositol 3-kinase (PI3K), found that the enzyme is a "class III" or "Vps34" PI3K, and that it is irreversibly inhibited by Fe2+-mediated covalent, nonspecific interactions with the leading antimalarial drug dihydroartemisinin (Hassett M. R., et al. (2017) Biochemistry 56, 4335-4345).

Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes

June 15, 2020 - 15:37 -- Open Access
Author(s): 
Li J, Zhang J, Cui L, et al.
Reference: 
PLoS Negl Trop Dis 14(6): e0008255

Vivax malaria is an important public health problem in the Greater Mekong Subregion (GMS), including the China-Myanmar border. Previous studies have found that Plasmodium vivax has decreased sensitivity to antimalarial drugs in some area of GMS, but the sensitivity of P. vivax to antimalarial drugs is unclear in the China-Myanmar border. Here, we investigate the drug sensitivity profile and genetic variations for two drug resistance related genes, in P. vivax isolates to provide baseline information for future drug studies in the China-Myanmar border.

NOT Open Access | Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

June 3, 2020 - 07:04 -- NOT Open Access
Author(s): 
da Silva Santos L, de Carvalho MFL, de Souza Pinto AC, da Fonseca AL, Dias Lopes JC, de Pilla Varotti F, de Freitas RP, Alves RB
Reference: 
Med Chem. 2020 Jun 2

Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs.

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