Synthesis of novel isoindole-containing phakellistatin 2 analogs and the conformation features affecting their antitumor activities

Two novel isoindole-doped cyclopeptide analogs of phakellistatin 2 with γ-turns were prepared. The compound with all D-Pro residues showed better antitumor activity against HepG-2 cells than that containing all L-Pro moieties, indicating the importance of the handedness of the conformation. LDH release tests showed that the compounds killed the cancer cells through a membrane disruption mechanism.