In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi
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 syntheti...
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| Language: | English |
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Wiley
2010-01-01
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| Series: | Journal of Parasitology Research |
| Online Access: | http://dx.doi.org/10.1155/2010/716498 |
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| author | David Wenkert Bernadette Ramirez Yuehai Shen Michael A. Kron |
| author_facet | David Wenkert Bernadette Ramirez Yuehai Shen Michael A. Kron |
| author_sort | David Wenkert |
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| description | 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. |
| format | Article |
| id | doaj-art-d02be237e2584f4e8284d35b1bf93fda |
| institution | Kabale University |
| issn | 2090-0023 2090-0031 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Parasitology Research |
| spelling | doaj-art-d02be237e2584f4e8284d35b1bf93fda2025-02-03T01:20:51ZengWileyJournal of Parasitology Research2090-00232090-00312010-01-01201010.1155/2010/716498716498In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayiDavid Wenkert0Bernadette Ramirez1Yuehai Shen2Michael A. Kron3The Department of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Biochemistry, University of the Philippines, Manila, PhilippinesThe Department of Physiology, Michigan State University, East Lansing, MI 48824, USABiotechnology and Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USAGeldanamycin (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.http://dx.doi.org/10.1155/2010/716498 |
| spellingShingle | David Wenkert Bernadette Ramirez Yuehai Shen Michael A. Kron In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi Journal of Parasitology Research |
| title | In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi |
| title_full | In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi |
| title_fullStr | In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi |
| title_full_unstemmed | In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi |
| title_short | In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi |
| title_sort | in vitro activity of geldanamycin derivatives against schistosoma japonicum and brugia malayi |
| url | http://dx.doi.org/10.1155/2010/716498 |
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