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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Synthesis, Cytotoxicity, Anti-Migration and Anti-Invasion Activity of Diphyllin Heterocyclic Derivatives

Author(s): Weidong Shen, Haijiao Chen, Miaomiao Wu, Ting Zhang, Li Zhu and Yu Zhao*

Volume 18, Issue 1, 2022

Published on: 21 December, 2020

Page: [122 - 129] Pages: 8

DOI: 10.2174/1573406417666201221160220


Background: Diphyllin, an arylnaphthalene lignan lactone, isolated from many traditional medicinal plants, has been reported to possess anticancer and antiviral activities. Natural diphyllin and its glycosides were identified as potent vacuolar H+-ATPase (V-ATPase) inhibitors.

Objective: The aim of this study was to design and synthesize a series of heterocyclic derivatives of diphyllin as novel anticancer agents.

Methods: The targeted heterocyclic derivatives of diphyllin were synthesized from diphyllin employing etherification reaction and N-substitution reaction. Cytotoxicity of these compounds on four cancer cells was assessed by MTT assay. The inhibitory activity of V-ATPase of compound 3n was measured on MGC-803 cells. Anti-migration and anti-invasion abilities were assessed by transwell invasion assay and scratch wound assay.

Results: Most of these derivatives displayed potent cytotoxicity on four cancer cells at submicromolar concentrations. The most potent derivative 3n has been shown to inhibit V-ATPase activity, migration and invasion abilities on MGC-803 cells at 0.75 μM.

Conclusion: The collective results clearly indicate that heterocyclic derivatives of diphyllin inhibit the viability, V-ATPase activity, migration and invasion of the MGC803 cells. The current findings provide valuable insights for the future development of novel diphyllin derivatives as anticancer agents.

Keywords: Diphyllin derivatives, heterocyclic derivatives, synthesis, cytotoxicity, anti-migration activity, anti-invasion activity.

Graphical Abstract
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