| Summary: | The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly<sup>5</sup> (compound <b>8</b>) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca<sup>2+</sup> concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound <b>8</b>. Western blotting tests showed that compound <b>8</b> could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides.
|
|---|