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.