Synthesis and Antitumor Activities of Glycine-exchanged Analogs of Spicamycin

Abstract

A series of SPM VIII analogs were synthesized to investigate the effect of the amino acid moiety on the antitumor activity. The L-threonine analog and the glycylglycine analog of SPM VIII showed much higher cytotoxity to P388 murine leukemia cells (IC₅₀ 5.8 nM and 0.11 nM, respectively) than SPM VIII (IC₅₀ 25 nM). However, replacement of the glycine moiety with other amino acids greatly reduced the antitumor activity against COL-1 human colon cancer xenograft model. This study indicated that the glycine moiety of SPM VIII is crucial for the antitumor effect.