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4,5-Diaryl imidazoles with hydroxamic acid appendages as anti-hepatoma agents

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Summary

Introduction Hepatocellular carcinoma (HCC) is the most abundant tumour of the liver with rising patient numbers in the Western world countries. Despite newly approved drugs like protein kinase inhibitors the survival rate is still poor. Methods In order to identify potential new drugs for the treatment of HCC we investigated the real-time cell viability, apoptosis induction (sub-G1 cells), and HDAC (histone deacetylase) activity of two hepatocellular cancer cell lines HepG2 and Hep3B treated with new imidazole-tethered hydroxamates. Results The tested cinnamyl hydroxamates exhibited significant antiproliferative and cytotoxic activity in HCC cells as apparent from high sub-G1 cell levels in flow cytometric cell cycle analyses. In Hep3B cells HDAC inhibition was observed comparable in magnitude to that induced by the clinically applied HDAC inhibitor SAHA (Zolinza, Vorinostat). Conclusions The new imidazolyl hydroxamic acids lend themselves as a possible alternative to SAHA in the therapy of HCC. Even more so since similar 4,5-diarylimidazoles lacking only the hydroxamate functionality were previously shown in animal studies to be well tolerated and orally applicable.

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Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, 35043, Marburg, Germany

    Pietro Di Fazio & Susanne Lingelbach

  2. Organic Chemistry Laboratory, University Bayreuth, 95440, Bayreuth, Germany

    Rainer Schobert & Bernhard Biersack

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  1. Pietro Di Fazio
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  2. Susanne Lingelbach
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  3. Rainer Schobert
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  4. Bernhard Biersack
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Correspondence to Bernhard Biersack.

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The online version of this article contains supplementary material (synthesis of imidazoles 1 and 2, real time cell viability of Hep3B cells), which is available to authorized users.

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Di Fazio, P., Lingelbach, S., Schobert, R. et al. 4,5-Diaryl imidazoles with hydroxamic acid appendages as anti-hepatoma agents. Invest New Drugs 33, 104–108 (2015). https://doi.org/10.1007/s10637-014-0188-0

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  • DOI: https://doi.org/10.1007/s10637-014-0188-0

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