Interaction of Chloroquine and Its Analogues with Heme: An Isothermal Titration Calorimetric Study

Bachhawat, Kiran; Thomas, Ciza; Surolia, Namita; Surolia, Avadhesha

doi:10.1006/bbrc.2000.3592

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…These findings agree closely with those obtained in 40% aqueous DMSO which indicate a log K of 5.5 for CQ at pH 7.5 and no significant effect of pH [9] or ionic strength [10]. By contrast, Surolia and co-workers have reported evidence for a two-site model with log K values of 5.1 and 8.1, respectively for low and high affinity sites at pH 7.4 and an ionic strength of 0.15 M [48]. This study suggested that association constants weaken markedly with decreasing pH and strengthen with ionic strength.…”

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionssupporting

confidence: 86%

“…2) [10]. The slope of this plot (a) for data obtained from 40% DMSO [9] and aqueous solution from Dorn et al [45] is identical (1.1 ± 0.1 and 1.0 ± 0.1, respectively), while that for the high affinity binding reported by Bachhawat et al [48] is 0.6 ± 0.1. The intercepts (TDS 0 ) are, respectively, 29 ± 2, 29 ± 5 and 23 ± 3 kJ/mol.…”

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 56%

“…It has also been used to investigate association of a series of square planar Pt(II) phenanthroline and bipyridyl complexes with Fe(III)PPIX, some of which show in vitro antimalarial activity [44]. The subsequent introduction of titration calorimetry into this field [45][46][47][48][49] has finally permitted measurement of the association constants in aqueous solution and permits comparison with data obtained in aqueous DMSO as well as nonaqueous solution. A listing of association constants for a selection of quinoline antimalarials obtained by different methods is provided in Table 1.…”

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 99%

“…Enthalpies and entropies of interaction have been obtained from titration calorimetry [45,[47][48][49] and temperature dependence of association constants in 40% aqueous DMSO [9]. Despite the similar trends in association constants and hence DG values in aqueous solution and aqueous DMSO, the trends in DH and DS are almost exactly opposite in these media.…”

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 99%

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Interactions of quinoline antimalarials with hematin in solution

Egan

2006

Journal of Inorganic Biochemistry

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Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionssupporting

confidence: 86%

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 56%

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 99%

Section: Thermodynamics Of Fe(iii)ppix-quinoline Interactionsmentioning

confidence: 99%

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Interactions of quinoline antimalarials with hematin in solution

Egan

2006

Journal of Inorganic Biochemistry

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“…The drug is believed to interact with haem (or its precursors) or to inhibit one of the enzymes involved in the synthesis if haem, possibly haem polymerase [172][173][174][175]. [186].…”

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confidence: 99%

Metabolic enzymes of helminth parasites: potential as drug targets

Timson¹

2015

CPPS

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Metabolic pathways which extract energy from carbon compounds are essential for an organism's survival. Therefore, inhibition of enzymes in these pathways represents a potential therapeutic strategy to combat parasitic infections. However, the high degree of similarity between host and parasite enzymes makes this strategy potentially difficult. Nevertheless, several existing drugs to treat infections by parasitic helminths (worms) target metabolic enzymes. These include the trivalent antimonials which target phosphofructokinase and Clorsulon which targets phosphoglycerate mutase and phosphoglycerate kinase. Glycolytic enzymes from a variety of helminths have been characterised biochemically, and some inhibitors identified. To date none of these inhibitors have been developed into therapies. Many of these enzymes are externalised from the parasite and so are also of interest in the development of potential vaccines. Less work has been done on tricarboxylic acid cycle enzymes and oxidative phosphorylation complexes. Again, while some inhibitors have been identified none have been developed into drug-like molecules. Barriers to the development of novel drugs targeting metabolic enzymes include the lack of experimentally determined structures of helminth enzymes, lack of direct proof that the enzymes are vital in the parasites and lack of cell culture systems for many helminth species. Nevertheless, the success of Clorsulon (which discriminates between highly similar host and parasite enzymes) should inspire us to consider making serious efforts to discover novel anthelminthics which target metabolic enzymes.

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Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity

Ortíz

Vásquez-Ocmín

Cojean

et al. 2020

Bioorganic Chemistry

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A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.

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Interaction of Chloroquine and Its Analogues with Heme: An Isothermal Titration Calorimetric Study

Cited by 24 publications

References 24 publications

Interactions of quinoline antimalarials with hematin in solution

Interactions of quinoline antimalarials with hematin in solution

Metabolic enzymes of helminth parasites: potential as drug targets

Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity

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