THE IN-VITRO HL-60 CELL - TRYPANOSOMA-BRUCEI-RHODESIENSE CULTURE SYSTEM - A RAPID IN-VITRO DRUG SCREEN

The in vitro culture system is described in which Trypanosoma brucei r hodesiense (LOUTat.1) was grown with the human feed layer cell HL-60. The use of this system in determining the 50% growth Inhibitory Concen tration (IC50) of unknown compounds for both the trypanosomes and the host cell was demonstrated. The data shows that several analogues of p entamidine have significantly reduced host cell toxicity but maintain or have increased typanocidal activity. The value of the trypanosome/H L-60 in vitro culture system as a rapid primary in vitro drug screen i s discussed. Based upon the ability of this primary screen to predict potential drug efficacy, several analogues screened in vitro were then tested in vivo. The results of the in vivo tests confirmed the abilit y of the in vitro screen to predict drug efficacy, and also suggests t hat better analogues of pentamidine (less host toxicity and greater tr ypanocidal activity) can be obtianed to treat human trypanosomiasis.