Advances in Chagas disease drug development: 2009-2010.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Buckner
Frederick S
FS
Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, Washington, 98195, USA. fbuckner@u.washington.edu
Navabi
Nazlee
N
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D058069:Neglected Diseases / Q000188:drug therapy / Q000469:parasitology; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
D000935:Antifungal Agents; D001688:Biological Products; D014344:Trypanocidal Agents