Table of Contents Author Guidelines Submit a Manuscript
Journal of Parasitology Research
Volume 2010, Article ID 716498, 7 pages
http://dx.doi.org/10.1155/2010/716498
Research Article

In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi

1The Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
2Department of Biochemistry, University of the Philippines, Manila, Philippines
3Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland
4Biotechnology and Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

Received 15 June 2010; Revised 22 October 2010; Accepted 23 November 2010

Academic Editor: Nirbhay Kumar

Copyright © 2010 David Wenkert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Geldanamycin (GA) is a benzoquinone-containing ansamycin that inhibits heat shock protein 90. GA derivatives are being evaluated as anti-neoplastic agents, but their utility against parasites whose heat shock proteins (Hsps) have homology with human Hsp90 is unknown. The activities of four synthetic GA derivatives were tested in vitro using adult Brugia malayi and Schistosoma japonicum. Two of the derivatives, 17-N-allyl-17-demethoxygeldanamycin (17-AAG) and 17-N-(2-dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), are currently in human clinical trials as anticancer drugs. Using concentrations considered safe peak plasma concentrations for these two derivatives, all four derivatives were active against both parasites. The less toxic derivative 17-AAG was as effective as GA in killing S. japonicum, and both DMAG and 5-bromogeldanoxazinone were more active than 17-AAG against B. malayi. This work supports continued evaluation of ansamycin derivatives as broad spectrum antiparasitic agents.