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 and leishmania. High in vitro antiparasitic activity was observed for some derivatives with one compound showing high activity against all three parasites (ED50 values of 0.02, 0.48 and 0.32 microM, for Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani, respectively). The lack of correlation between inhibitory activity against TR and ED50 values suggests that TR is not the target.
Chibale
K
K
Department of Chemistry, University of Cape Town, South Africa. chibale@psipsy.uct.ac.za
Visser
M
M
Yardley
V
V
Croft
S L
SL
Fairlamb
A H
AH
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014966:Xanthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D014966:Xanthenes; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase