In VitroActivity of Geldanamycin Derivatives againstSchistosoma japonicumandBrugia malayi

[摘要] 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 testedin vitrousing adultBrugia malayiandSchistosoma 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 killingS. japonicum, and both DMAG and 5′-bromogeldanoxazinone were more active than 17-AAG againstB. malayi.This work supports continued evaluation of ansamycin derivatives as broad spectrum antiparasitic agents.

[学科分类] 神经科学