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Issue 29, 2013
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Design and biological characterization of hybrid compounds of curcumin and thalidomide for multiple myeloma

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Abstract

In our efforts to develop effective treatment agents for human multiple myeloma (MM), a series of hybrid molecules based on the structures of thalidomide (1) and curcumin (2) were designed, synthesized, and biologically characterized in human multiple myeloma MM1S, RPMI8226, U266 cells, and human lung cancer A549 cells. The biological results showed that two hybrid compounds, 5 and 7, exhibited significantly improved lethal effects towards all three human MM cell models compared to 1 or 2 alone, as well as the combination of 1 and 2. Furthermore, mechanistic studies in U266 cells demonstrated that 5 and 7 can induce the production of reactive oxygen species (ROS) and cause G1/S arrest, thus leading to apoptosis and cell death. Additionally, they exhibited inhibitory effects on NFκB activation in A549 cells. Collectively, the results obtained from these hybrid compounds strongly encourage their further optimization as new leads to develop effective treatment agents for human MM.

Graphical abstract: Design and biological characterization of hybrid compounds of curcumin and thalidomide for multiple myeloma

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Publication details

The article was received on 25 Mar 2013, accepted on 07 Jun 2013 and first published on 11 Jun 2013


Article type: Communication
DOI: 10.1039/C3OB40595H
Citation: Org. Biomol. Chem., 2013,11, 4757-4763
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    Design and biological characterization of hybrid compounds of curcumin and thalidomide for multiple myeloma

    K. Liu, D. Zhang, J. Chojnacki, Y. Du, H. Fu, S. Grant and S. Zhang, Org. Biomol. Chem., 2013, 11, 4757
    DOI: 10.1039/C3OB40595H

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