The membranolytic action of lead cyclic peptides 15c and 16c was accessed by conducting a calcein dye leakage assay using lipid vesicles mimicking bacterial and mammalian membranes. The fluorescent dye leakage experiments showed that both 15c and 16c induced a concentration-dependent dye leakage when treated with bacterial membranemimicking liposomes. At 50 µg/mL, cyclic peptides 15c and 16c resulted in the leakage of 56-64% of dye after 20 min exposure to bacterial mimicking liposomes and induced 100% dye release after 60 min and 50 min, respectively. At the lowest experimental concentration (5 µg/mL), both cyclic peptides (15c and 16c) exerted the disruption of lipid vesicles as indicated by 38% of dye release after 50 min incubation (Figures and).