Synthesis of Novel N-Branched Acyclic Nucleoside Phosphonates As Potent and Selective Inhibitors of Human, Plasmodium falciparum and Plasmodium vivax 6-Oxopurine Phosphoribosyltransferases

2012 ◽  
Vol 55 (13) ◽  
pp. 6209-6223 ◽  
Author(s):  
Dana Hocková ◽  
Dianne T. Keough ◽  
Zlatko Janeba ◽  
Tzu-Hsuan Wang ◽  
John de Jersey ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Selective Inhibitors ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Human Plasmodium

Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases

ChemMedChem ◽  
2017 ◽  
Vol 12 (14) ◽  
pp. 1133-1141 ◽  
Author(s):  
Martin Maxmilian Kaiser ◽  
Ondřej Baszczyňski ◽  
Dana Hocková ◽  
Lenka Poštová-Slavětínská ◽  
Martin Dračínský ◽  
...  
Keyword(s):  
Selective Inhibitors ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Membered Heterocycle

scholarly journals Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephen D. Woolley ◽  
Louise Marquart ◽  
John Woodford ◽  
Stephan Chalon ◽  
Joerg J. Moehrle ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Haematological Response ◽  
Relative Contribution ◽  
Cell Counts ◽  
Plasmodium Vivax Malaria ◽  
Pre Treatment ◽  
Peak Parasitaemia ◽  
Human Plasmodium ◽  
Blood Stage Malaria

Abstract Background Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. Methods This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. Results The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566–27,815), 71,427 parasites/ml [IQR 33,236–180,213], and 34,840 parasites/ml (IQR 13,302–77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8–13.3), 14.8% (IQR 11.8–15.9) and 11.7% (IQR 8.9–14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5–21), 15 (IQR 7–22), and 8 (IQR 7–15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1–5.3), 7.2% (IQR 5.8–7.8), and 4.9% (IQR 3.7–6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006–0.06), 0.128% (IQR 0.068–0.616) and 0.022% (IQR 0.008–0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Conclusion Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.

Inhibition of the in vitro growth of Plasmodium falciparum by acyclic nucleoside phosphonates

1999 ◽  
Vol 12 (1) ◽  
pp. 53-61 ◽  
Author(s):  
L.J.J.W. Smeijsters ◽  
F.F.J. Franssen ◽  
L. Naesens ◽  
E. de Vries ◽  
A. Holý ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Vitro Growth ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside
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