Chemical formula |
C21H33N3O.2HCl (dihydrochloride) |
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Physical properties |
Octanol/water partition coefficient: LogP = 5.84 |
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Molecular weight:
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Solubility |
Dihydrochloride: water soluble (> 100 mg/ml at 25 °C) |
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Ethanol soluble |
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Chemical characteristics |
Weak base pKa =
4.2 (quinoline nitrogen)
10.4 (amine side chain)
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Behaviour in biological fluids |
Affinity for proteins (Duenas et al., 2007) |
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Interaction with host cell / parasite |
Affinity for negative phospholipids (Duenas et al., 2007) |
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Morphology alteration of Leishmania (Langreth et al., 1983) |
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Uptake and accumulation in |
Electrical gradient diffusion (Duenas et al., 2007) |
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Leishmania donovani promastigotes |
No affinity for sterols (Soares et al., 2010) |
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No transporter suspected (López-Martín et al., 2008) |
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Energy dependent efflux (Soares et al., 2010) |
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Intracellular targets |
Accumulation in acidocalcisomes (Vercesi et al., 2000) |
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Rapid collapse of the mitochondrial inner-membrane potential (Vercesi et al., 2002) |
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Sitamaquine susceptibility not related to accumulation into acidocalcisomes (López-Martín et al., 2008) |
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Bioavailability |
Plasma half-life: 26.1 hr |
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4-CH2OH as major urinary metabolite (Theoharides et al., 1987) |
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Clinical trials Phase II |
High efficacy rate at doses 1.5-3 mg/kg/day × 28 by oral route |
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Trials in India (Jha et al., 2005) |
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Trials in kenya (Wasunna et al., 2005) |
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Toxicity / adverse effects (% of patients) |
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(Jha et al., 2005) |
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No methemoglobinemia in Kenya (Wasunna et al., 2005) |
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Resistance |
At risk: obtained in vitro (Bories et al., 2008) |