7-O-aminoalkyl-2,3-dehydrosilibinins: Synthesis and in vitro Anti-cancer Efficacy

Author(s): Da-You Ma, Li-Chao Zhang, Kun-Jian Peng, Jiang Zeng, Li-Jun Liu, Zhi-Yong Luo*, Su-You Liu*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 18 , Issue 8 , 2018

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Graphical Abstract:


Background: The heptaprotective flavonolignan silibinin and dehydrosilibinin have exhibited moderate antiproliferative activities toward many cancer cell lines. Considering of the nontoxic profile of these natural products, chemical modification to enhance the anticancer potentials is promising.

Method: A series of 7-O-aminoalkyl-2,3-dehydrosilibinin derivatives were synthesized and evaluated for their antiproliferative activities against several cancer cell lines.

Results: A number of the synthesized dehydrosilibinin derivatives exhibited greatly enhanced potency with 50% growth inhibition at low micromolar concentrations. Structure activity study indicated that the distance between N and 7-O on the side chain has a limited influence on the antiproliferative activity, while the presence of a morpholino group decreases the antiproliferative activities dramatically. Flow cytometry based assays on human colon cancer HCT116 cells revealed that 6a and 6c, two of the most potent derivatives, effectively arrested the cell cycle in the G2 phase and stimulated cell apoptosis.

Conclusion: Our findings suggest that attaching an appropriate tertiary amino alkyl side chain through 7-Oalkylation on 2,3-dehydrosilibinin, would be a viable strategy for the development of silibinin derivatives as anticancer agents.

Keywords: Dehydrosilibinin, antiproliferative activity, synthesis, derivatives, 7-O-aminoalkyl-2, 3-dehydrosilibinins, low micromolar concentrations, flow cytometry.

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Article Details

Year: 2018
Published on: 02 April, 2018
Page: [1156 - 1162]
Pages: 7
DOI: 10.2174/1871520618666180402122713
Price: $65

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