Halofuginone - the multifaceted molecule.

Abstract

Halofuginone is an analog of febrifugine-an alkaloid originally isolated from the plant Dichroa febrifuga. During recent years, halofuginone has attracted much attention because of its wide range of beneficial biological activities, which encompass malaria, cancer, and fibrosis-related and autoimmune diseases. At present two modes of halofuginone actions have been described: (1) Inhibition of Smad3 phosphorylation downstream of the TGFβ signaling pathway results in inhibition of fibroblasts-to-myofibroblasts transition and fibrosis. (2) Inhibition of prolyl-tRNA synthetase (ProRS) activity in the blood stage of malaria and inhibition of Th17 cell differentiation thereby inhibiting inflammation and the autoimmune reaction by activation of the amino acid starvation and integrated stress responses. This review deals with the history and origin of this natural product, its synthesis, its known modes of action, and it's various biological activities in pre-clinical animal models and in humans.

• Authors: Mark Pines, Itai Spector
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 1 Pg. 573-94 (Jan 05 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25569515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antimalarials
• Antineoplastic Agents
• Antiprotozoal Agents
• Piperidines
• Quinazolinones
• halofuginone

Topics

• Animals
• Antimalarials (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Antiprotozoal Agents (therapeutic use)
• Apoptosis (drug effects)
• Clinical Trials as Topic
• Humans
• Piperidines (chemical synthesis, therapeutic use)
• Quinazolinones (chemical synthesis, therapeutic use)