Synthesis and activity of β-carboline antimalarials targeting the Plasmodium falciparum heat shock 90 protein

Neil K Viswanathan; Michael E Chirgwin; Julia Gibbs; Brianna N Kalaj; Sierra Durham; Jennifer Tran; Maximillian Gomez; Horacio Lazaro; Ming Chen; Christopher R Mansfield; Emily R Derbyshire; Scott Eagon

doi:10.1016/j.bmcl.2023.129410

Synthesis and activity of β-carboline antimalarials targeting the Plasmodium falciparum heat shock 90 protein

Bioorg Med Chem Lett. 2023 Aug 15:92:129410. doi: 10.1016/j.bmcl.2023.129410. Epub 2023 Jul 20.

Authors

Affiliations

¹ Department of Chemistry & Biochemistry, California Polytechnic State University, San Luis Obispo, CA 93407, USA.
² Department of Chemistry, Duke University, Durham, NC 27708, USA.
³ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Department of Food Science and Technology, University of California, Davis, Davis, CA 95616, USA.
⁵ Promega Biosciences, 277 Granada Drive, San Luis Obispo, CA 93401, USA.
⁶ Department of Molecular Genetics and Microbiology, Duke School of Medicine, Durham, NC 27708, USA.
⁷ Department of Chemistry & Biochemistry, California Polytechnic State University, San Luis Obispo, CA 93407, USA. Electronic address: seagon@calpoly.edu.

PMID: 37478957
DOI: 10.1016/j.bmcl.2023.129410

Abstract

A collection of β-carbolines based on the natural product harmine, a compound known to target the heat shock 90 protein of Plasmodium falciparum, was synthesized and tested for antimalarial activity and potential toxicity. Several of these novel compounds display promising bioactivity, providing a new potential therapeutic with a mode of action that differs versus any currently available clinical treatment.

Keywords: Beta-carbolines; Heat shock 90 protein; Malaria; Plasmodium falciparum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimalarials* / pharmacology
Carbolines / pharmacology
Heat-Shock Response
Plasmodium falciparum

Substances

Antimalarials
Carbolines