Antimalarial activity of tetrahydro-β-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein.
Department of Chemistry and Biochemistry, California Polytechnic State University, San Luis Obispo, CA 93407, USA. Electronic address: [email protected]
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40508, USA.
Department of Chemistry and Biochemistry, California Polytechnic State University, San Luis Obispo, CA 93407, USA.
Promega Biosciences, 277 Granada Drive, San Luis Obispo, CA 93401, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Public Health, Tauro University, Vallejo, CA 94592, USA.
Department of Food Science and Technology, University of California Davis, Davis, CA 95616, USA.
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
- Published Article
Bioorganic & medicinal chemistry letters
- Publication Date
Aug 18, 2020
A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment. Copyright © 2020 Elsevier Ltd. All rights reserved.
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This record was last updated on 10/16/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/32822760