Synthetic and antitumor comparison of 9-O-alkylated and carbohydrate-modified berberine derivatives


Berberine is a naturally occurring isoquinoline alkaloid with moderate antitumor effect. It has been proved that berberine can affect the microenvironment of cancer cells, which is critical for cancer therapy and improving human immunity. Therefore, structural modification of berberine to obtain derivatives with high antitumor effect attracts the great attention of scientists. This paper describes the synthesis and in vitro antitumor investigation of some 9-O-alkylated and carbohydrate-modified berberine derivatives using high efficient strategy. The cytotoxicity investigation was accomplished on different cancer cell lines by the well-optimized MTT assay, and the results indicated that 9-O-hydrophobic modified berberine derivative 9 with long lipid chain showed promising in vitro antitumor activity with the IC50 value as low as 4.87 ± 0.24 μM. Percentage of apoptosis was measured by a Hoechst 33342/PI staining strategy on HeLa cells, which revealed that compound 9 could induce 84% of cell apoptosis at very low concentration (5 μM). Flow cytometry analysis indicated that compound 9 might inhibit HeLa cell proliferation by G2 phase arrest. The expression of various cell apoptosis proteins was measured by western blot analysis, and the results indicated that compound 9 could induce over-expression of Caspase-3, Parp, and Bax and down-regulate the expression of P53 and PCNA. All these data indicated the high potential of compound 9 for developing novel anticancer drugs.

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This research was supported by grants from the Young Science Foundation of Shandong Academy of Sciences (No. 2020QN0018), the Young Doctoral Cooperation Foundation of Qilu University of Technology (Shandong Academy of Sciences) (No. 201713SH2024), the Natural Science Foundation of Shandong Province (No. ZR2018PB007 and No. ZR2016YL009), the High-end Talents Program of Jinan (No. 2019GXRC044), and the Jinan High-end Foreign Experts Recruitment Program (No. 2019T10).

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Correspondence to Kechun Liu or Lizhen Wang.

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Wang, R., Rostyslav, S., Li, X. et al. Synthetic and antitumor comparison of 9-O-alkylated and carbohydrate-modified berberine derivatives. J IRAN CHEM SOC (2020).

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  • Berberine
  • HeLa cell
  • Antitumor
  • Alkylated
  • Carbohydrate