Firestone R A, Pisano J M, Bonney R J
J Med Chem. 1979 Sep;22(9):1130-3. doi: 10.1021/jm00195a026.
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.
pK值在大约5到9之间的胺类是溶酶体亲和性的，因为溶酶体是细胞内的酸性区室。如果这类胺带有长的疏水链，它们在溶酶体内质子化后会变成去污剂，使溶酶体膜破裂并杀死细胞。已经制备了六种溶酶体亲和性胺类，它们的表现都符合预期。它们对所有含有溶酶体的细胞具有细胞毒性，但对缺乏溶酶体的红细胞没有毒性。它们的作用方式、烷基链长度对活性的影响，以及它们的细胞毒性作用仅在细胞内浓度高于阈值时才出现，这些都支持了它们作为溶酶体亲和性去污剂的观点。潜在应用之一是癌症化疗。
