The in vitro HL-60 cell--Trypanosoma brucei rhodesiense culture system: a rapid in vitro drug screen.

Abstract

The in vitro culture system is described in which Trypanosoma brucei rhodesiense (LOUTat.1) was grown with the human feed layer cell HL-60. The use of this system in determining the 50% growth Inhibitory Concentration (IC50) of unknown compounds for both the trypanosomes and the host cell was demonstrated. The data shows that several analogues of pentamidine have significantly reduced host cell toxicity but maintain or have increased typanocidal activity. The value of the trypanosome/HL-60 in vitro culture system as a rapid primary in vitro drug screen is 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 ability of the in vitro screen to predict drug efficacy, and also suggests that better analogues of pentamidine (less host toxicity and greater trypanocidal activity) can be obtained to treat human trypanosomiasis.