Organic & Biomolecular Chemistry

Issue 29, 2013

The international home of synthetic, physical and biomolecular organic chemistry.

Communication

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

Kai Liu,^a Datong Zhang,^b Jeremy Chojnacki,^a Yuhong Du,^c Haian Fu,^c Steven Grant^d and Shijun Zhang*^a

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Org. Biomol. Chem., 2013,11, 4757-4763

DOI: 10.1039/C3OB40595H
Received 25 Mar 2013, Accepted 07 Jun 2013
First published online 11 Jun 2013

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.