Identification of an acridine photoaffinity probe for trypanocidal action.
Twenty-four acridine derivatives were screened for trypanocidal activity in Trypanosoma brucei in order to determine which structural features of the acridine molecule confer maximal antiparasitic activity. The synthesis of several new azidoacridine derivatives are also reported as well as an assessment of their value as possible photoaffinity probes for the study of acridine trypanocidal action. The most effective and selective acridine trypanocides, with and without irradiation, were the 3-amino-10-methylacridinium salt derivatives. With brief irradiation, one azidoacridine, 3-amino-6-azido-10-methylacridinium chloride, showed considerable trypanocidal activity at very limiting drug concentrations (10(-7)M) and warrants consideration as a possible photoaffinity probe.
D000166:Acridines / Q000494:pharmacology*; D000345:Affinity Labels / Q000138:chemical synthesis; D000818:Animals; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010775:Photic Stimulation; D010777:Photochemistry; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D000166:Acridines; D000345:Affinity Labels; D014344:Trypanocidal Agents