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Article
Open AccessPopulation pharmacokinetics of primaquine and its metabolites in African males
Primaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard ...
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Article
Open AccessComparative pharmacokinetics and tissue distribution of primaquine enantiomers in mice
Primaquine (PQ) has been used for the radical cure of relapsing Plasmodium vivax malaria for more than 60 years. PQ is also recommended for prophylaxis and prevention of transmission of Plasmodium falciparum. How...
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Article
First in class (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders
Newly designed pyrrolo[2,1-c][1,4]benzodiazepines tricyclic skeleton has shown potential clusters of cannabinoid receptors CB1/CB2 selective ligands. CB2 plays a critical role in microglial-derived neuroinflam...
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Article
Open AccessFormation primaquine-5,6-orthoquinone, the putative active and toxic metabolite of primaquine via direct oxidation in human erythrocytes
The activity and haemolytic toxicity associated with primaquine has been linked to its reactive metabolites. The reactive metabolites are thought to be primarily formed through the action of cytochrome P450-media...
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Chapter
Drug Discovery from Complex Mixtures: Serendipity, Screening, and Characterization
Natural products mixtures, as originally sourced in nature, are encountered in complex matrices that may contain useful active components at low concentrations, but also a number of unrelated molecular compone...
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Chapter
Raw Materials Production and Manufacturing Process Control Strategies
Strategies for the of complex mixture drugs are illustrated using plant-derived complex products and are comprised of unique challenges in the management of raw materials supply chains as well as the contr...
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Article
Open AccessMetabolism of primaquine in normal human volunteers: investigation of phase I and phase II metabolites from plasma and urine using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry
Primaquine (PQ), an 8-aminoquinoline, is the only drug approved by the United States Food and Drug Administration for radical cure and prevention of relapse in Plasmodium vivax infections. Knowledge of the metabo...
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Article
Open AccessInhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads
Protein ubiquitylation is an important post-translational regulation, which has been shown to be necessary for life cycle progression and survival of Plasmodium falciparum. Ubiquitin is a highly conserved 76 amin...
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Article
Open AccessPathway-specific inhibition of primaquine metabolism by chloroquine/quinine
There has been some evidence to suggest that the addition of chloroquine (CQ) or quinine (QN) to 8-aminoquinoline (8-AQ) treatment regimens may increase the therapeutic efficacy of the 8-AQ and simultaneously ...
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Article
Open AccessDiversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum
A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products f...
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Article
Open AccessDifferential kinetic profiles and metabolism of primaquine enantiomers by human hepatocytes
The clinical utility of primaquine (PQ), used as a racemic mixture of two enantiomers, is limited due to metabolism-linked hemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehyd...
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Article
Evaluation of wild yam (Dioscorea villosa) root extract as a potential epigenetic agent in breast cancer cells
The present study was designed to evaluate the efficacy of wild yam root extract (WYRE) as a potential demethylating agent using two breast cancer cell lines, MCF-7 (estrogen receptor positive; ER+) and MDA-MB-23...
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Article
Open AccessEnantioselective metabolism of primaquine by human CYP2D6
Primaquine, currently the only approved drug for the treatment and radical cure of Plasmodium vivax malaria, is still used as a racemic mixture. Clinical use of primaquine has been limited due to haemolytic toxic...
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Article
Open AccessIn vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine
Several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. Tigecycline, a semi-synthetic deriv...
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Article
Open AccessTafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds
Tafenoquine (TQ) is an 8-aminoquinoline (8AQ) that has been tested in several Phase II and Phase III clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. NPC-1161...
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Article
Open AccessThe metabolism of primaquine to its active metabolite is dependent on CYP 2D6
The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns t...
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Article
Open AccessCYP450 phenoty** and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine
The 8-aminoquinoline (8AQ) drug primaquine (PQ) is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as ...
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Article
Silencing of tissue factor by antisense deoxyoligonucleotide prevents monocrotaline/LPS renal injury in mice
Tissue factor (TF) is involved in monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity. It is not known whether MCT/LPS can cause renal toxicity and whether TF is involved in this toxicity. Thus, the pr...
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Article
Oxidized low-density lipoprotein and tissue factor are involved in monocrotaline/lipopolysaccharide-induced hepatotoxicity
These studies were aimed at characterizing an animal model of inflammation-induced hepatotoxicity that would mimic features of idiosyncratic liver toxicity observed in humans. An attempt was made to identify o...
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Article
Open AccessPotential utility of natural products as regulators of breast cancer-associated aromatase promoters
Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and...
