Energy-linked protonation of quinacrine in beef heart submitochondrial membranes

Huang, Cheng-Schen; Kopacz, Stephan J.; Lee, Chuan-Pu

doi:10.1016/0005-2728(77)90025-1

Cited by 20 publications

(10 citation statements)

References 18 publications

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“…The fluorescence intensities (Em 500) at the three excitation peaks increased with increasing pH (Fig. 2B), in accordance with the pH-dependent increase in the relative fluorescence quantum yield (31). Thus, deprotonation of nitrogen in the ring with a pH increase contributes to the fluorescence increase (Figs.…”

Section: Structures and Physicochemical Properties Of Qc Change Drastsupporting

confidence: 77%

“…These estimations suggest that the lipophilicities of the antimalarial drugs change drastically in response to pH-dependent structural change compared with CPZ. by spectral analysis (31). However, it is unclear which structure the spectrum reflects and the significance of water on structural change.…”

Section: Structures and Physicochemical Properties Of Qc Change Drastmentioning

confidence: 99%

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Antimalarial drugs lose their activity with a slight drop in pH

Kitagawa

Mastumoto

Terashima

et al. 2020

Preprint

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Antimalarial drugs have antimicrobial, antiviral, antimalarial and immunosuppressive activities, although the mechanisms remain unknown. Quinacrine (QC) increases the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localizes in membranes and induces glucose starvation by noncompetitively inhibiting glucose uptake. A logarithmic increase in antimicrobial activity with pH-dependent CAD formation was also observed for chloroquine, indicating that the CAD structure is crucial for its pharmacological activity. A decrease in CAD structure with a slight decrease in pH from 7.4 greatly reduced their effects; namely, these drugs would inefficiently act on falciparum malaria and COVID-19 pneumonia patients with acidosis, resulting in resistance. Recovering normal blood pH or using pH-insensitive quinoline drugs might be effective.

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Section: Structures and Physicochemical Properties Of Qc Change Drastsupporting

confidence: 77%

Section: Structures and Physicochemical Properties Of Qc Change Drastmentioning

confidence: 99%

Antimalarial drugs lose their activity with a slight drop in pH

Kitagawa

Mastumoto

Terashima

et al. 2020

Preprint

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“…The red-shift of the emission wavelength is due to the Stokes shift, where QC loses excitation energy via radiation-less deactivation by molecular motion (Figure B,C). The fluorescence intensities (Em500) at the three excitation peaks increased with pH (Figure B,D), in accordance with the pH-dependent increase in the relative fluorescence quantum yield . Thus, deprotonation of nitrogen in the ring with a pH increase contributes to the fluorescence increase.…”

Section: Resultssupporting

confidence: 71%

Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH

et al. 2021

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Quinacrine (QC) and chloroquine (CQ) have antimicrobial and antiviral activities as well as antimalarial activity, although the mechanisms remain unknown. QC increased the antimicrobial activity against yeast exponentially with a pHdependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localized in the yeast membranes and induced glucose starvation by noncompetitively inhibiting glucose uptake as antipsychotic chlorpromazine (CPZ) did. An exponential increase in antimicrobial activity with pH-dependent CAD formation was also observed for CQ, indicating that the CAD structure is crucial for its pharmacological activity. A decrease in CAD structure with a slight decrease in pH from 7.4 greatly reduced their effects; namely, these drugs would inefficiently act on falciparum malaria and COVID-19 pneumonia patients with acidosis, resulting in resistance. The decrease in CAD structure at physiological pH was not observed for quinine, primaquine, or mefloquine. Therefore, restoring the normal blood pH or using pH-insensitive quinoline drugs might be effective for these infectious diseases with acidosis.

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“…We have used two different aminoacridine fluorescent dyes, quinacrine and ACMA, to monitor Suc-induced proton movements and membrane energization (Kraayenhof, 1970(Kraayenhof, , 1980Huang et al, 1983), but only quinacrine fluorescence responded to pH changes in media devoid of any membranes (results not shown) and could be used as a pH indicator (Huang et al, 1977(Huang et al, , 1983Kopacz et al, 1985). ACMA, a pH-dependent fluorescent dye of high sensitivity (Dufour et al, 1982;Greutert and Keller, 1993), exhibited a significant fluorescence quench in the presence of membranes as a response to changing energization states of the membranes (Huang et al, 1983; this report, "Results").…”

Section: Monitoring Of H+ Pump Activitymentioning

confidence: 99%

Characteristics of Sucrose Transport and Sucrose-Induced H+ Transport on the Tonoplast of Red Beet (Beta vulgaris L.) Storage Tissue

Getz

Klein

1995

Plant Physiol.

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Sucrose-induced changes of the energization state of the red beet root (Beta vulgaris L. ssp. conditiva) vacuolar membrane were observed with the fluorescent dyes 6-chloro-9-{[4-(diethylamino)-1 -methylbutyll-aminol-2-methoxyacridine dihydrochloride, as a pH monitor, and 9-amino-6-chloro-2-methoxyacridine (ACMA). Consequently, transient acidification of the surrounding suspension medium could be measured with a pH electrode. This signal was specific for Suc and was not seen for sorbitol, mannitol, or maltose. Sucrose-induced medium acidification was sensitive to the same inhibitors that were efficient i n inhibiting sucrose transport, including the monoclonal antibodies TNP, , -, , and C50-5.3. It was seen with vacuoles and vesicles energized with MgATP before sucrose was added but also with vacuoles not artificially energized previously. Using bafilomycin A, for the inhibition of the vacuolar ATPase of vacuoles previously energized by MgATP, apparent K, values for H + export from the vacuoles to the medium could be calculated taking into account the passive proton leak. Apparent K, values for H + export determined from data obtained with pH measurements in the medium and with ACMA corresponded to those obtained previously for sucrose uptake. Comparing sucrose uptake rates with corresponding H+ export rates at the respective sucrose concentrations and at K , , a stoichiometry of approximately one proton per transported sucrose was estimated.

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Energy-linked protonation of quinacrine in beef heart submitochondrial membranes

Cited by 20 publications

References 18 publications

Antimalarial drugs lose their activity with a slight drop in pH

Antimalarial drugs lose their activity with a slight drop in pH

Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH

Characteristics of Sucrose Transport and Sucrose-Induced H+ Transport on the Tonoplast of Red Beet (Beta vulgaris L.) Storage Tissue

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