| Abstract
| - Less toxic drugs are needed to combat the human parasite Trypanosoma cruzi (Chagas'sdisease). One novel target for antitrypanosomal drug design is farnesyltransferase. Severalfarnesyltransferase inhibitors based on the benzophenone scaffold were assayed in vitro andin vivo with the parasite. The common structural feature of all inhibitors is an amino functionwhich can be protonated. Best in vitro activity (LC50 values 1 and 10 nM, respectively) wasrecorded for the R-phenylalanine derivative 4a and for the N-propylpiperazinyl derivative 2f.These inhibitors showed no cytotoxicity to cells. When tested in vivo, the survival rates ofinfected animals receiving the inhibitors at 7 mg/kg body weight/day were 80 and 60% at day115 postinfection, respectively.
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