While several studies have explored how systematic modifications to a cyclic peptide backbone affect cell permeability, it is uncommon to combine this data with information on the biological activity of the molecule. One reason for this is that such modifications, despite improving membrane permeability, can cause significant changes to the peptide's overall properties. Another contributing factor is the frequent use of model peptides that lack known biological activity. In this work, we aimed to assess the extent to which the introduced fragments impacted the biological activity of the macrocycles. Since its discovery no biological activity has been reported for Sanguinamide A, making it hard to identify a cellular read-out that could potentially be connected to its membrane permeability. Therefore, we subjected our set of compounds to the cell painting assay that is agnostic towards specific biological targets. In this assay, cells are treated with compound followed by staining with various orthogonal dyes that highlight a variety of cellular elements. After imaging of the cells in the different dye channels, image analysis is performed to characterize morphological changes of the dyed cell components. The parameters obtained from this analysis are compared to those from a DMSO control and a morphological profile is generated. Such profiles can then be compared to each other (within a set of compounds) or to the profiles of a set of reference compounds with known activity.