Antimalarial drugs lose their activity with a slight drop in pH

Kitagawa, T.; Mastumoto, A.; Terashima, I.; Uesono, Y.

doi:10.1101/2020.08.04.237255

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bioRxiv · 10.1101/2020.08.04.237255

Antimalarial drugs lose their activity with a slight drop in pH

Kitagawa, T.·Mastumoto, A.·Terashima, I.·Uesono, Y.

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Abstract

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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Kitagawa, T., Mastumoto, A., Terashima, I., Uesono, Y.. 2020-08-05. Antimalarial drugs lose their activity with a slight drop in pH. https://doi.org/10.1101/2020.08.04.237255

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