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New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells

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Abstract

Purpose

Emerging evidence clearly suggests the potential chemopreventive and anti-tumor activity of a well known “natural agent” curcumin. However, studies have shown that curcumin is not readily bioavailable, and thus the tissue bioavailability of curcumin is also poor except for gastrointestinal track. Because of the potential biological activity of curcumin, many studies have attempted for making a better analog of cucumin that is equally effective or better with increased bioavailability, which was the purpose of our current study.

Methods

We have designed and synthesized new difluoro Knoevenagel condensates of curcumin and Schiff bases along with their copper (II) complexes and evaluated their biological activities with respect to the inhibitory effects on purified rabbit 26S proteasome, and growth inhibition and induction of apoptosis in colon and pancreatic cancer cell lines.

Results

All copper complexes possess distorted square planar geometries with 1:1 metal to ligand stoichiometry with reversible copper redox couple. The difluoro compound CDF exhibited inhibitory effects on purified rabbit 20S proteasome or cellular 26S proteasome, and caused both growth inhibition of cancer cell lines and induced apoptotic cell death in our preliminary assessment.

Conclusion

Our results suggest that our newly synthesized classes of curcumin analogs could be useful as chemopreventive and/or therapeutic agents against cancers.

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Authors and Affiliations

  1. D.Y.Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018, India

    Subhash Padhye, Abeda Jamadar & Deepak Chavan

  2. Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 John R, Detroit, Michigan, 48201, USA

    Huanjie Yang, Qiuzhi Cindy Cui, Kristin Dominiak, Jaclyn McKinney, Sanjeev Banerjee, Q. Ping Dou & Fazlul H. Sarkar

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  1. Subhash Padhye
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  2. Huanjie Yang
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Correspondence to Fazlul H. Sarkar.

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Dou and Sarkar are senior authors in this manuscript.

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Padhye, S., Yang, H., Jamadar, A. et al. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells. Pharm Res 26, 1874–1880 (2009). https://doi.org/10.1007/s11095-009-9900-8

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  • DOI: https://doi.org/10.1007/s11095-009-9900-8

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