Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
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

Abstract

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.

« Previous Next »
Graphical Abstract

[1]
Ling, Y.; Wang, X.M.; Wang, C.N.; Xu, C.J.; Zhang, W.; Zhang, Y.H.; Zhang, Y.A. Hybrids from Farnesylthiosalicylic Acid and Hydroxamic Acid as Dual Ras‐Related Signaling and Histone Deacetylase (HDAC) Inhibitors: Design, Synthesis and Biological Evaluation. ChemMedChem, 2015, 10, 971-976.
[2]
Chen, G.T.; Yang, M.; Nong, S.J.; Yang, X.; Ling, Y.; Wang, D.G.; Wang, X.Y.; Zhang, W. Microbial transformation of 20(S)-protopanaxadiol by Absidia corymbifera. Cytotoxic activity of the metabolites against human prostate cancer cells. Fitoterapia, 2013, 84, 6-10.
[3]
Chen, G.T.; Li, J.; Yang, S.S.; Lin, H.J.; Wu, J.J.; Zhai, X.G.; Song, Y.; Li, J.L. Biotransformation of 20(R)-panaxatriol by Mucor racemosus and the anti-hepatic fibrosis activity of some products. Nat. Prod. Res., 2017, 31, 1880-1885.
[4]
Yang, B.; Tao, H.M.; Qin, X.C.; Wang, Z.; Dong, J.D.; Lin, X.P.; Zhou, X.F.; Li, J.L.; Tu, Z.C.; Liu, Y.H. Aspergone, a new chromanone derivative from fungus Aspergillus sp. SCSIO41002 derived of mangrove soil sample. J. Antibiot. , 2017, 70, 788-790.
[5]
Yang, Y.; Islam, S.; Wang, J.; Li, Y.; Chen, X. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int. J. Biol. Sci., 2020, 16, 1708-1717.
[6]
Ren, J.L.; Zhang, A.H.; Wang, X.J. Traditional Chinese medicine for COVID-19 treatment. Pharmacol. Res., 2020, 155104743
[7]
Okigawa, M.; Maeda, T.; Kawano, N. The isolation and structure of three new lignans from Justicia procumbens Linn. var. leucanthahonda. Tetrahedron, 1970, 26, 4301-4305.
[8]
Shen, W.D.; Zou, X.P.; Chen, M.; Liu, P.F.; Shen, Y.H.; Huang, S.L.; Guo, H.M.; Zhang, L.L. Effects of Diphyllin as A Novel V-ATPase Inhibitor on Gastric Adenocarcinoma. Eur. J. Pharmacol., 2011, 667, 330-338.
[9]
Chen, H.W.; Cheng, J.X.; Liu, M.T.; King, K.; Peng, J.Y.; Zhang, X.Q.; Wang, C.H.; Shresta, S.; Schooley, R.T.; Liu, Y.T. Inhibitory and combinatorial effect of diphyllin, a V-ATPase blocker, on influenza viruses. Antiviral Res., 2013, 99, 371-382.
[10]
Asano, J.; Chiba, K.; Tada, M.; Yoshii, T. Antiviral activity of lignans and their glycosides from Justicia procumbens. Phytochemistry, 1996, 713-717.
[11]
Sorensen, M.G.; Henriksen, K.; Wulff, A.V.; Dziegiel, M.H.; Karsdal, M.A. J. Bone Miner. Res., 2007, 22, 1640-1648.
[12]
Zhang, Z.T.; Ma, J.L.; Zhu, L.; Zhao, Y. Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H+-ATPase inhibitors. Eur. J. Med. Chem., 2014, 82, 466-471.
[13]
McGuire, C.; Cotter, K.; Stransky, L.; Forgac, M. Regulation of V-ATPase assembly and function of V-ATPases in tumor cell invasiveness. Biochim. Biophys. Acta, 2016, 1857, 1213-1218.
[14]
Sautin, Y.Y.; Lu, M.; Gaugler, A.; Zhang, L.; Gluck, S.L. Phosphatidylinositol 3-kinase-mediated effects of glucose on vacuolar H+-ATPase assembly, translocation, and acidification of intracellular compartments in renal epithelial cells. Mol. Cell. Biol., 2005, 25, 575-589.
[15]
Cai, R.; Zhu, L.; Shen, W.D.; Zhao, Y. Synthesis, Cytotoxicity and Anti-invasion Activity of Three Natural Diphyllin L-arabinopyranosides. Fitoterapia, 2019, 137104198

Rights & Permissions Print Cite
Article Metrics
75
3
© 2024 Bentham Science Publishers | Privacy Policy