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Cited by 673

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease

Open access
Korth, Carsten, May, Barnaby C. H., Cohen, Fred E., Prusiner, Stanley B.·2001·Proceedings of the National Academy of Sciences

Abstract

Prion diseases in humans and animals are invariably fatal. Prions are composed of a disease-causing isoform (PrP Sc ) of the normal host prion protein (PrP C ) and replicate by stimulating the conversion of PrP C into nascent PrP Sc . We report here that tricyclic derivatives of acridine and phenothiazine exhibit half-maximal inhibition of PrP Sc formation at effective concentrations (EC 50 ) between 0.3 μM and 3 μM in cultured cells chronically infected with prions. The EC 50 for chlorpromazine was 3 μM, whereas quinacrine was 10 times more potent. A variety of 9-substituted, acridine-based analogues of quinacrine were synthesized, which demonstrated variable antiprion potencies similar to those of chlorpromazine and emphasized the importance of the side chain in mediating the inhibition of PrP Sc formation. Thus, our studies show that tricyclic compounds with an aliphatic side chain at the middle ring moiety constitute a new class of antiprion reagents. Because quinacrine and chlorpromazine have been used in humans for many years as antimalarial and antipsychotic drugs, respectively, and are known to pass the blood–brain barrier, we suggest that they are immediate candidates for the treatment of Creutzfeldt–Jakob disease and other prion diseases.

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Metadata

Authors
Korth, C., May, B. C. H., Cohen, F. E., & Prusiner, S. B.
Venue
Proceedings of the National Academy of Sciences
Published
2001-08-14
Volume
98
Issue
17
Pages
9836-9841
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2135301408
Cited by
673
References
38
FWCI
16.50
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. https://app.cochat.ai/papers/10.1073/pnas.161274798
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Korth, C., May, B. C. H., Cohen, F. E., & Prusiner, S. B. (2001). Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.161274798

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