Drug resistance in trapanososmes: cross-resitance analyses

Eight strains of Trypanosoma rhodesiense, made resistant respectively to atoxyl, butarsen, acriflavine, stilbamidine, Surfen C, suramin, and pontamine sky blue 5BX, have been examined for cross-resistance to representatives of nine structurally dissimilar groups of trypanocide. On the basis of their predominant ionic form at blood pH, these groups are considered in three main classes: (a) feebly ionized (neutral aromatic arsenicals), (b) ionized as cations (melaminyl arsenicals and antimonials, acridine derivatives, diguanidines and diamidines, 6-aminoquinoline and 6-aminocinnoline derivatives, phenanthridinium derivatives, triphenylmethane dyes), and (c) ionized as anions (carboxylated aromatic arsenicals and sulphonated naphthylamine derivatives). The results are discussed in relation to those of other workers and to possible modes of trypanocidal drug action. Cross-resistance behaviour is not wholly explicable on an ionic basis; the results suggest that stereospecific structural changes associated with initial drug uptake occur in resistant trypanosomes.