Melanoma markers based on both N-(2-dialkylaminoethyl)benzamides and lysosomotropic agents comprise a N-(2-dialkylaminoethyl)aminocarbamoyl pharmacophore, suggesting that
benzamides and lysosomotropic probes should show affinity to
melanoma and acidic cell organelles. We prepared novel fluorescent N-(2-dialkylaminoethyl)benzamides to prove this presumption. Lysosomotropic probes showed a
melanin affinity comparable to
benzamides. Lysosomal markers and
benzamides colocalized in acidic organelles. Various nonmelanoma cell lines showed equal
benzamide uptake and retention compared with
melanoma cells. In nonmelanoma cells the amount of retained
benzamides correlates with the number of acidic cell organelles.
Benzamides almost completely failed to accumulate in
melanoma cells with neutralized acidic organelles but normal
melanin content. In
melanoma retention of
benzamides, acidic cell organelles are the main determinant. N-(2-dialkylaminoethyl)benzamides are lysosomotropic probes with high accumulation in nonmelanoma
tumors with many acidic cell organelles. Alkylating
benzamides were reported previously to show a
melanoma unselective, in general enhanced cytotoxicity. Alkylating
benzamides can act as lysosomotropic
detergents or as
DNA alkylators. The ability of alkylating
benzamides to disrupt the membrane of lysosomes and cause liberation of lysosomal-trapped
fluorescent dyes was demonstrated by fluorescence microscopy. Whether they act as an
alkylating agent or a lysosomotropic
detergent in a specific cell line is dependent on the amount of acidic cell organelles. In cell lines with small amounts of acidic cell organelles alkylating
benzamides act as
alkylating agents, whereas in cell lines with many acidic cell organelles they act as lysosomotropic
detergents. In cell lines with high amounts of acidic cell organelles they do not reach the nucleus.