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

Hindawi Publishing Corporation Journal of Parasitology Research Volume 2010, Article ID 716498, 7 pages doi:10.1155/2010/716498 Research Article In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi David Wenkert,1 Bernadette Ramirez,2, 3 Yuehai Shen,1 and Michael A. Kron4 1 The Department of Physiology, Michigan State University, East Lansing, MI 48824, USA 2 Department of Biochemistry, University of the Philippines, Manila, Philippines 3 Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland 4 Biotechnology and Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA Correspondence should be addressed to David Wenkert, wenkert@ 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. 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