2001
DOI: 10.1124/mol.59.5.1298
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Diamidine Compounds: Selective Uptake and Targeting inPlasmodium falciparum

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Cited by 97 publications
(127 citation statements)
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“…Based on kinetic and pharmacological inhibitor profiles of isosmotic hemolysis and radiolabel flux experiments, several quaternary ammonium compounds have been demonstrated to permeate P. falciparum-infected erythrocytes via the parasite-induced new permeation pathway (NPP [11,22]). Similarly, diamidine compounds, which-being highly charged and hydrophilic-are structurally comparable to the bis-quaternary ammonium compounds, have also been demonstrated to enter the host erythrocyte via the NPP (23). In this study, we have investigated the mechanism of entry and antimalarial activity of a newly synthesized bis-quaternary ammonium compound, T16 (1,12-dodecanemethylene bis[4-methyl-5-ethylthiazolium] diodide; Fig.…”
mentioning
confidence: 99%
“…Based on kinetic and pharmacological inhibitor profiles of isosmotic hemolysis and radiolabel flux experiments, several quaternary ammonium compounds have been demonstrated to permeate P. falciparum-infected erythrocytes via the parasite-induced new permeation pathway (NPP [11,22]). Similarly, diamidine compounds, which-being highly charged and hydrophilic-are structurally comparable to the bis-quaternary ammonium compounds, have also been demonstrated to enter the host erythrocyte via the NPP (23). In this study, we have investigated the mechanism of entry and antimalarial activity of a newly synthesized bis-quaternary ammonium compound, T16 (1,12-dodecanemethylene bis[4-methyl-5-ethylthiazolium] diodide; Fig.…”
mentioning
confidence: 99%
“…Another potential explanation for our results with ester borrelidin derivatives is that these compounds may offer increased selectivity due to better permeability in infected erythrocytes. Malaria parasites have been shown to increase erythrocyte permeability to ions, organic solutes, and antimalarial drugs through new permeation pathways that are associated to P. falciparum infection (54)(55)(56)(57). Further work is needed to determine the role of permeability differences in the selectivity of borrelidin analogs.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, DB289 has been shown to possess good in vivo activity against malaria in the mouse and in vitro activity against various Plasmodium strains, such that it is currently undergoing clinical trials for all these disease conditions. Normal human erythrocytes are impermeable to diamidine drugs, but those infected with P. falciparum are not, by virtue of a new porous pathway induced in the host cell membrane by the parasite itself (Ginsburg et al, 1983;Stead et al, 2001). …”
mentioning
confidence: 99%