Antitrypanosomal action enhanced by photoaffinity labeling with ethidium analogs.

The trypanocidal activity of photoreactive azido analogs of ethidium was tested to determine the suitability of using such compounds as in vivo probes to study the mechanism of the antitrypanosomal activity of ethidium. Eight ethidium analogs, including three nonphotoreactive compounds, were tested for their ability to kill T. brucei both with and without photolytic activation. Two analogs tested, the monoamino-monoazido isomers, showed greater that 100-fold enhancement of trypanocidal activity following photolytic activation in situ. Without photolytic activation, only the nonphotoreactive monoamino precursor analogs showed activity greater than the parent ethidium compound. The availability of suitable ethidium analogs which can be covalently attached by in situ photoactivation provides a new approach for studying the mechanism by which ethidium exerts its trypanocidal activity.