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Design, synthesis, and biological evaluation of novel 2,4-thiazolidinedione derivatives as histone deacetylase inhibitors targeting liver cancer cell line

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Abstract

As a part of an ongoing effort to find alternate chemotherapeutic agents for hepatocellular carcinoma, we herein, report the design and synthesis of two novel compounds targeting histone deacetylase (HDAC) with 2,4-thiazolidinedione as zinc chelating group. Further, we demonstrate that these compounds show cytotoxicity that parallels their ability to inhibit HDACs activity in human liver cancer cell line HepG2. The findings obtained in this study indicate that 2,4-thiazolidinedione group may be utilized successfully to inhibit HDAC activity with future potential for lead optimization by chemical derivatization of active compound, N-(6-(2,4-dioxothiazolidin-3- yl)hexyl) benzenesulfonamide.

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Acknowledgments

Dr C. S. Ramaa thanks Board of Research in Nuclear Sciences (BRNS), BARC, Mumbai, India (Sanction Number: 2006/37/41/BRNS) for financial support. Ms. Rhea Mohan is grateful to Board of Research in Nuclear Sciences (BRNS) for providing fellowship. We thank Dr. V. J. Kadam, Principal, Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai for providing support for the ongoing project. The authors would also like to express their gratitude to Mr. Bharat S. Khade, Scientific Assistant ‘D’, ACTREC, for technical support during the tenure of this work.

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Authors have no conflict of interest regarding the work reported in this manuscript.

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Correspondence to Sanjay Gupta or C. S. Ramaa.

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Mohan, R., Sharma, A.K., Gupta, S. et al. Design, synthesis, and biological evaluation of novel 2,4-thiazolidinedione derivatives as histone deacetylase inhibitors targeting liver cancer cell line. Med Chem Res 21, 1156–1165 (2012). https://doi.org/10.1007/s00044-011-9623-3

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