Photo-induced synthesis and antitumor activity of marine zygosporamide analogs containing the isoindolinone fragment

Abstract

Marine cyclic peptides have become an important source for drug development. In this work, two novel cyclic peptide zygosporamide analogs with the isoindolinone fragment were prepared, which have broad-spectrum antitumor activity. We have tried to compare their bioactivities by changing the amino acid (R-³Leu and S-⁴Leu) configuration. Notably, compound 8, with R-³Leu and S-⁴Leu residues, showed better inhibiting ability than that of compound 9, which contains S-³Leu and R-⁴Leu residues. Furthermore, careful molecular docking indicated that compound 8 presented stronger binding with the EGFR protein of liver cancer cells, providing an explanation for the difference in bioactivity. This research has provided a useful guide for peptide-based drug-target design.