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antimalarial drugs

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.

NOT Open Access | Nanoemulsion composed of 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol), a synthetic analog of 3-alkylpiridine marine alkaloid: development, characterization, and antimalarial activity

June 2, 2020 - 09:17 -- NOT Open Access
Author(s): 
Da Silva MGD, Cardoso JF, Da Silva GRD, et al.
Reference: 
European Journal of Pharmaceutical Sciences, Volume 151, 1 August 2020, 105382

Malaria treatment is based on a reduced number of antimalarial drugs, and drug resistance has emerged, leading to the search for new antimalarial drugs incorporated into pharmaceutical formulations. In this study, 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol) (thiazoline), a synthetic analog of 3-alkylpiridine marine alkaloid, and a potent antimalarial substance, was incorporated into O/W nanoemulsion.

NOT Open Access | Malaria Parasite Clearance: What Are We Really Measuring

May 7, 2020 - 13:30 -- NOT Open Access
Author(s): 
Khoury DS, Zaloumis SG, Grigg MJ, Haque A, Davenport MP; Interdisciplinary Approaches to Malaria Consortium
Reference: 
Trends Parasitol. 2020 May;36(5):413-426

Antimalarial drugs are vital for treating malaria and controlling transmission. Measuring drug efficacy in the field requires large clinical trials and thus we have identified proxy measures of drug efficacy such as the parasite clearance curve.

Antimalarial drugs impact chemical messenger secretion by blood platelets

May 4, 2020 - 14:01 -- Open Access
Author(s): 
Xiong-Hang K, He J, Kemnetz-Ness K, Haynes C
Reference: 
Biochem Biophys Rep. 2020 Apr 22;22:100758

Advances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response.

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

April 13, 2020 - 14:01 -- NOT Open Access
Author(s): 
Sissoko A, Vasquez-Ocmin P, Duval RA, et al.
Reference: 
ACS Infect Dis. 2020 Apr 8

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

Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis

December 23, 2019 - 16:09 -- Open Access
Author(s): 
Naing C, Whittaker MA, Htet NH, Aye SN, Mak JW
Reference: 
PLoS ONE 14(12): e0225882

The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.

Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo

November 18, 2019 - 16:15 -- Open Access
Author(s): 
Sergey Kapishnikov, Trine Staalsø, Yang Yang, Jiwoong Lee, Ana J. Pérez-Berná, Eva Pereiro, Yang Yang, Stephan Werner, Peter Guttmann, Leslie Leiserowitz, and Jens Als-Nielsen
Reference: 
PNAS November 12, 2019 116 (46) 22946-22952

The most widely used antimalarial drugs belong to the quinoline family. Their mode of action has not been characterized at the molecular level in vivo. We report the in vivo mode of action of a bromo analog of the drug chloroquine in rapidly frozen Plasmodium falciparum-infected red blood cells.

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