Quantification of Intracellular Accumulation and Retention of Lysosomotropic Macrocyclic Compounds by High-Throughput Imaging of Lysosomal Changes.

Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far.

Lysosomotropic cationic amphiphilic drugs inhibit adipocyte differentiation in 3T3-L1K cells via accumulation in cells and phospholipid membranes, and inhibition of autophagy.

Some cationic amphiphilic drugs (CADs) have been individually reported to interfere with the differentiation of immune system cells, such as macrophages and dendritic cells. To investigate the possible generic nature of this process, in this study we aimed to see whether these drugs are capable of interfering with the differentiation of adipocytes. Further, we investigated whether this feature might be connected to the lysosomotropic character of these drugs, and their disturbance of intracellular membrane trafficking rather than to the individual pharmacologic properties of each drug.