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Synthesis and evaluation of a series of novel imidazolidinone analogues of 6-aminoflavone as anticancer and anti-inflammatory agents

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Abstract

The flavone moiety is a potential pharmacophore known for its diverse range of pharmacological activities. Aminoflavones have recently been the subject of considerable attention as lead molecules in several cancer research projects. Imidazolidinone heterocycles represent another biologically active scaffold with known cytotoxic properties. In an attempt to provide synergistic cytotoxic activity, these two moieties have been combined, and the resulting novel analogues evaluated for their anticancer and anti-inflammatory activities. The results revealed that the cytotoxicities of these compounds were fivefold greater than those of aminoflavone. DNA histograms obtained from cell cycle analysis in the presence of these compounds were apoptotic in their nature. Furthermore, the in vivo screening of these compounds using Ehrlich’s ascites tumour model showed an increase in life span, whereas an in vivo anti-inflammatory study resulted in the enhancement of the anti-inflammatory potential. The results therefore supported the hypothesis that there is a relationship between inflammation and cancer.

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Acknowledgments

The authors would like to acknowledge the All India Council for Technical Education (AICTE) of New Delhi for funding this work under Quality Improvement Programme (QIP). The authors would also like to thank Dr. Annapurni Rangarajan from the Department of Molecular Reproduction Development and Genetics (MRDG) at the Indian Institute of Science in Bangalore for providing the facility to perform the cytotoxicity assays, and the Hoechst staining and flow cytometric FACS analyses. The authors would also like to acknowledge the NMR Research centre at the Indian Institute of Science IISC in Bangalore for the NMR spectral data.

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Authors and Affiliations

  1. Department of Pharmaceutical Quality Assurance, MCOPS, Manipal University, Manipal, India

    Sudheer Moorkoth

  2. Department of Pharmaceutical Chemistry, MCOPS, Manipal University, Manipal, India

    K. K. Srinivasan & Alex Joseph

  3. Department of Pharmacology, MCOPS, Manipal University, Manipal, India

    N. Gopalan Kutty & M. Naseer

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  1. Sudheer Moorkoth
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Correspondence to Sudheer Moorkoth.

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Moorkoth, S., Srinivasan, K.K., Gopalan Kutty, N. et al. Synthesis and evaluation of a series of novel imidazolidinone analogues of 6-aminoflavone as anticancer and anti-inflammatory agents. Med Chem Res 22, 5066–5075 (2013). https://doi.org/10.1007/s00044-013-0486-7

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