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 D. Durham, Jennifer Tran, Maximillian J. Gomez, Horacio Lazaro, Ming Chen, Christopher R. Mansfield, Emily R. Derbyshire, Scott Eagon
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.
Topics & Concepts
Plasmodium falciparumChemistryHarmineNatural productPharmacologyHeat shock proteinMode of actionIn vitroMalariaBiochemistryImmunologyBiologyGeneSynthesis and bioactivity of alkaloidsToxin Mechanisms and ImmunotoxinsSynthesis and Biological Evaluation