Advances in Chagas disease drug development: 2009-2010

Curr Opin Infect Dis. 2010 Dec;23(6):609-16. doi: 10.1097/QCO.0b013e3283402956.

Abstract

Purpose of review: The need for better drugs to treat patients with Chagas disease remains urgent. This review summarizes the advancements in drug development over the past 2 years.

Recent findings: Drug development efforts are almost exclusively occurring as preclinical research, although phase II studies for the antifungal drug, posaconazole, and a prodrug of ravuconazole are being planned. Several recent laboratory investigations demonstrate anti-Trypanosoma cruzi activity of novel small molecules in animal models. These include nonpeptidic cruzain inhibitors, novel inhibitors of the sterol 14α-demethylase enzyme, new compounds (arylimidamides) related to pentamidine, derivatives of nifurtimox, compounds using ruthenium complexes, and several natural products. The recent implementation of a high-throughput screen of more than 300 000 compounds against intracellular T. cruzi amastigotes done at the Broad Institute is an important development, yielding approximately 300 selective inhibitors, many of which may serve as leads for medicinal chemistry efforts.

Summary: Progress is slow, but recent advancements in both drug development and advocacy for research on neglected diseases are encouraging. Efforts to define a target product profile and to harmonize methodologies for testing drugs for Chagas disease are described herein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use*
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Biological Products / therapeutic use*
  • Chagas Disease / drug therapy*
  • Chagas Disease / parasitology
  • Disease Models, Animal
  • Drug Discovery / methods*
  • Humans
  • Molecular Targeted Therapy
  • Neglected Diseases / drug therapy
  • Neglected Diseases / parasitology
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / enzymology

Substances

  • Antifungal Agents
  • Biological Products
  • Trypanocidal Agents