A series of SPM VIII analogs were synthesized to investigate the effec
t of the amino acid moiety on the antitumor activity. The L-threonine
analog and the glycylglycine analog of SPM VIII showed much higher cyt
otoxity to P388 murine leukemia cells (IC50 5.8 nM and 0.11 nM, respec
tively) than SPM VIII (IC50 25 nM). However, replacement of the glycin
e moiety with other amino acids greatly reduced the antitumor activity
against COL-1 human colon cancer xenograft model. This study indicate
d that the glycine moiety of SPM VIII is crucial for the antitumor eff
ect.