Inhibitors of the plasmodial surface anion channel as antimalarials
Inventors
Desai, Sanjay A. • Pillai, Ajay D.
Assignees
US Department of Health and Human Services
Publication Number
US-10881669-B2
Publication Date
2021-01-05
Expiration Date
2029-07-15
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Abstract
Disclosed are inhibitors of the plasmodial surface anion channel (PSAC) inhibitors and the use thereof in treating or preventing malaria in an animal such as a human, comprising administering an effective amount of an inhibitor or a combination of inhibitors. An example of such an inhibitor is a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R1 to R7 are as described herein.
Core Innovation
The invention relates to inhibitors of the plasmodial surface anion channel (PSAC) and their use in treating or preventing malaria in animals, including humans. The compounds of the invention are represented by specific chemical formulas (I, IV, and V) and can be administered alone or in combination to enhance the killing of malaria parasites. These compounds act by inhibiting PSAC, which is essential for parasite survival within human red blood cells.
Malaria is a major infectious disease caused by Plasmodium parasites with significant morbidity and mortality worldwide, especially in African children. Current treatments rely on antimalarial drugs, but resistance to existing drugs necessitates the development of new therapies. PSAC has been identified as a molecular mechanism altering infected red blood cell permeability, facilitating parasite nutrient uptake necessary for growth and survival.
The PSAC displays unique properties including selective exclusion of sodium ions and permeability to various nutrients and solutes required by the parasite. Because PSAC is located on the erythrocyte membrane, it offers an accessible drug target that avoids issues of drug resistance linked to extrusion from parasite compartments. The invention provides new compounds targeting PSAC, including compounds that inhibit two distinct channel components (A and B), which exhibit synergistic parasite killing when used in combination.
Claims Coverage
The patent includes one independent claim defining a pharmaceutical composition.
Pharmaceutical composition including specific PSAC inhibitor compounds
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound selected from the specified chemical formulas that inhibit the plasmodial surface anion channel (PSAC). These compounds correspond to the defined formula groups I, IV, and V or their pharmaceutically acceptable salts, enabling the prevention or treatment of malaria.
The independent claim covers pharmaceutical compositions containing PSAC inhibitor compounds characterized by their specific chemical structures and their use as antimalarial agents to prevent or treat malaria.
Stated Advantages
The compounds exhibit synergistic parasite killing when used in combination, achieving enhanced efficacy greater than the sum of individual effects.
PSAC's surface location on infected red blood cells provides direct access to inhibitors, reducing the likelihood of drug resistance via extrusion mechanisms.
The compounds specifically target a critical transporter for parasite nutrient acquisition, offering a novel mechanism for combating malaria.
Documented Applications
Preventing or treating malaria in animals, including humans, by administering effective amounts of compounds that inhibit the plasmodial surface anion channel (PSAC).
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