NeoN-methylsansalvamide is a novel low-molecular-weight cyclic pentadepsipeptide that exerts cytotoxic effects on various human
cancer cell lines. Its structural analysis using liquid chromatography mass/mass spectrometry showed the cyclic structure sequence -
phenylalanine-
leucine-
valine-N-methylleucine-leucic
acid-. The intrinsic cytotoxic and multidrug resistance reversal effects of
neoN-methylsansalvamide were evaluated on the human
cancer cell lines MES-SA and HCT15 as well as on their multidrug resistance sublines (MES-SA/DX5 and HCT15/CL05, respectively) using the
sulforhodamine B assay. The EC50 values of
paclitaxel for MES-SA, HCT15, and for the multidrug resistance sublines MES-SA/DX5 and HCT15/CL05 were 1.00±0.20, 0.85±0.63, 10.00±0.53, and >1000 nmol/l, respectively. However, the EC50 values for
paclitaxel including 3 μmol/l
neoN-methylsansalvamide for MES-SA/DX5, HCT15, and HCT15/CL02 were 1.58±0.12, 0.10±0.02, and 288.40±21.02 nmol/l, respectively. The in-vitro multidrug resistance reversal activity of
neoN-methylsansalvamide was similar to that of the control
verapamil. These finding suggests that a novel cyclic pentadepsipeptide,
neoN-methylsansalvamide, is effective in reversing multidrug resistance in vitro, and this activity may be a major applicable biological function of this compound.