SYNTHESIS AND ANTITUMOR ACTIVITIES OF GLYCINE-EXCHANGED ANALOGS OF SPICAMYCIN

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.