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p.falciparum

Anopheles ecology, genetics and malaria transmission in northern Cambodia

March 24, 2021 - 14:09 -- Open Access
Author(s): 
Vantaux A, Riehle MM, Witkowski B, et al.
Reference: 
Sci Rep. 2021 Mar 19;11(1):6458

In the Greater Mekong Subregion, malaria cases have significantly decreased but little is known about the vectors or mechanisms responsible for residual malaria transmission. We analysed a total of 3920 Anopheles mosquitoes collected during the rainy and dry seasons from four ecological settings in Cambodia (villages, forested areas near villages, rubber tree plantations and forest sites). Using odor-baited traps, 81% of the total samples across all sites were collected in cow baited traps, although 67% of the samples attracted by human baited traps were collected in forest sites. Overall, 20% of collected Anopheles were active during the day, with increased day biting during the dry season.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes

March 23, 2021 - 14:35 -- Open Access
Author(s): 
Coelho CH, Tang WK, Duffy PE, et al.
Reference: 
Nat Commun. 2021 Mar 19;12(1):1750

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites.

Not Open Access | Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion

March 17, 2021 - 09:37 -- NOT Open Access
Author(s): 
Nguyen W, Dans MG, Sleebs BE, et al.
Reference: 
Eur J Med Chem. 2021 Mar 15;214:113253

The emerging resistance to combination therapies comprised of artemisinin derivatives has driven a need to identify new antimalarials with novel mechanisms of action. Central to the survival and proliferation of the malaria parasite is the invasion of red blood cells by Plasmodium merozoites, providing an attractive target for novel therapeutics. A screen of the Medicines for Malaria Venture Pathogen Box employing transgenic P. falciparum parasites expressing the nanoluciferase bioluminescent reporter identified the phenylsulfonyl piperazine class as a specific inhibitor of erythrocyte invasion.

NOT Open Access | 3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

March 17, 2021 - 09:06 -- NOT Open Access
Author(s): 
Luczywo A, González LG, Mellado M, et al.
Reference: 
Nat Prod Res. 2021 Mar 11:1-7

Malaria is an infectious illness, affecting vulnerable populations in Third World countries. Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. So, eighteen oxindole derivatives, aza analogues were obtained with moderate to excellent yields. Also, the saturated derivatives of oxindole and aza derivatives via H2/Pd/C reduction were obtained in good yields, leading to racemic mixtures of each compound.

NOT Open Access | Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues

February 25, 2021 - 10:13 -- NOT Open Access
Author(s): 
Saini A, Kumar S, Raj R, Chowdhary S, Gendrot M, Mosnier J, Fonta I, Pradines B, Kumar V
Reference: 
Bioorg Chem. 2021 Feb 16;109:104733

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities.

A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites

February 9, 2021 - 10:02 -- Open Access
Author(s): 
Cobb DW, Kudyba HM, Villegas A, Hoopmann MR, Baptista RP, Bruton B, Krakowiak M, Moritz RL, Muralidharan V
Reference: 
PLoS Pathog. 2021 Feb 3;17(2):e1009293

Malaria remains a major global health problem, creating a constant need for research to identify druggable weaknesses in P. falciparum biology. As important components of cellular redox biology, members of the Thioredoxin (Trx) superfamily of proteins have received interest as potential drug targets in Apicomplexans. However, the function and essentiality of endoplasmic reticulum (ER)-localized Trx-domain proteins within P. falciparum has not been investigated.

Is malaria parasite ex-vivo viability reduction really "superior" to observed parasite clearance rate

December 29, 2020 - 15:06 -- Open Access
Author(s): 
White NJ, Watson JA
Reference: 
J Infect Dis. 2020 Dec 28:jiaa790

Ina study of 10 P. falciparum infected volunteers with submicroscopic parasitemias given a single 200mg dose of artesunate, Rebelo et al (1) report a substantial difference in the ex-vivo growth of sequentially sampled circulating ring stage(2) parasites comparing infections with artemisin insensitive (Pfkelch wild type) and artemisinin resistant(PfkelchR539T)parasites.

Not Open Access | Nanotized curcumin-benzothiophene conjugate: A potential combination for treatment of cerebral malaria

October 13, 2020 - 12:50 -- NOT Open Access
Author(s): 
Ghosh A, Banerjee T
Reference: 
IUBMB Life. 2020 Oct 9.

The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone.

NOT Open Access | Synthesis, structure-activity relationship and antimalarial efficacy of 6-chloro-2-arylvinylquinolines

September 23, 2020 - 09:30 -- NOT Open Access
Author(s): 
Huang G, Murillo Solano C, Yuan Y, et al.
Reference: 
J Med Chem. 2020 Sep 22

There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound.

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