Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents
Shimei Xiao,
Zhiqiang Wang,
Huanli Zhang,
Lei Zhao,
Qingran Chang,
Xiong Zhang,
Rui Yan,
Xiaodan Wu,
Yingxue Jin
Affiliations
Shimei Xiao
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Zhiqiang Wang
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Huanli Zhang
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Lei Zhao
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Qingran Chang
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Xiong Zhang
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Rui Yan
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Xiaodan Wu
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
Yingxue Jin
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China
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 Gly5 (compound 8) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca2+ concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound 8. Western blotting tests showed that compound 8 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.
