NOT Open Access | Recrudescence of P.falciparum malaria in a migrant treated by tocilizumab
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J Travel Med. 2021 Mar 23:taab043
No abstract available
p.falciparum
Anopheles ecology, genetics and malaria transmission in northern Cambodia
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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
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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
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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
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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
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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
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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
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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
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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
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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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