Synthesis and evaluation of 9,9-dimethylxanthene tricyclics against trypanothione reductase, Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani

Derivatives of 9,9-dimethylxanthene were synthesised and evaluated against trypanothione reductase (TR) and in vitro against parasitic trypanosomes an d leishmania. High in vitro antiparasitic activity was observed for some de rivatives with one compound showing high activity against all three parasit es (ED50 values of 0.02, 0.48 and 0.32 mu M, for Trypanosoma brucei, Trypan osoma cruzi, and Leishmania donovani, respectively). The lack of correlatio n between inhibitory activity against TR and ED50 values suggests that TR i s not the target. (C) 2000 Elsevier Science Ltd. All rights reserved.