Lysosomotropic agents. 1. Synthesis and cytotoxic action of lysosomotropic detergents.
Amines whose pK values lie between about 5 and 9 are lysosomotropic because lysosomes are acidic intracellular compartments. If such amines bear long hydrophobic chains, they become detergents upon protonation inside the lysosomes, rupturing the lysosomal membrane and killing the cell. Six types of lysosomotropic amines have been prepared that all behave in the expected manner. They are cytotoxic to all lysosome-bearing cells but not red blood cells, which lack lysosomes. Their mode of action, the effect of alkyl chain length on activity, and the fact that their cytotoxic action appears only above a threshhold intracellular concentration support the belief that they behave as lysosomotropic detergents. Among the potential applications is cancer chemotherapy.
D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003902:Detergents / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D012515:Mast-Cell Sarcoma / Q000648:ultrastructure; D051379:Mice; D009374:Neoplasms, Experimental / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D000588:Amines; D003902:Detergents