Triazinyl derivatives that are potent inhibitors of glucose transport in Trypanosoma brucei.
Glucose transport in Trypanosoma brucei is facilitated by a transporter that is kinetically markedly different from its mammalian homologue. In this regard, the trypanosomal transporter may be selectively targeted. We investigated the potential of a series of triazinyl derivatives as inhibitors of glucose transport in T. brucei. A graded response of glucose transporter inhibition by these compounds was observed, with Cibacron blue 3GA, CiB, being the most potent. This inhibited transport by up to 90% in a concentration-dependent manner, with an IC50 of about 19.4 microM. A Dixon plot of different concentrations of this triazine and the rate of transport suggested that inhibition may be simple and competitive. The inhibition constant Ki was 14.8 microM. Although cytochalasin B has been widely reported to inhibit glucose uptake by mammalian and other eukaryotic glucose transporters, it had no effect at all on the trypanosome transporter at concentrations equivalent to those of the triazines. This may suggest structural differences between the trypanosome and mammalian glucose transporters and also suggests that the triazine moiety may serve as a template for the design potent trypanocides targeted at the glucose transporter.
Bayele
H K
HK
Department of Biochemistry, University of Bath, UK. h.bayele@rfc.ucl.ac.uk
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism
D014227:Triazines; C012842:Cibacron Blue F 3GA; D005947:Glucose