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Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines

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Abstract

Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids and cyclic amines (\(N\)-Me-piperazine, imidazole, 2-Me-imidazole, and indole) was tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361) in vitro. Compounds exerted antiproliferative activity in the high to the single-digit micromolar concentrations, causing increase of the cell population fraction in S phase and apoptosis. \(N\)-Me-piperazine and imidazole derivatives of aroylacrylic acids substituted with bulky alkyl substituents (2,4-di-\(i\)-Pr-Ph-, 2,4,6-tri-Et-Ph-, or \(\beta \)-tetrahydronaphthyl-) showed the best potency, while indole adducts were proved as the inferior antiproliferative agents. Few compounds showed significant selectivity, tumor versus healthy cells, with selectivity index \({\sim }60\) for the most selective congener. An unbiased in silico distinction between more and less potent compounds was obtained from 3D QSAR models derived by alignment-independent GRIND-2 descriptors.

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Acknowledgments

This work is supported by the Ministry of Education, Science and Technological Development of Serbia, under Grant 172035. Authors gratefully acknowledge OpenEye Scientific Software, Santa Fe, NM, for the free academic licensing of software tools.

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Authors and Affiliations

  1. Department of Chemistry – IChTM, University of Belgrade, Njegoševa 12, 11000 , Belgrade, Serbia

    Ivan O. Juranić & Branko J. Drakulić

  2. Laboratory for Conservation and Restoration, National Archive of Serbia, Karnegijeva 2, 11000 , Belgrade, Serbia

    Ana V. Tošić

  3. Institute for Oncology and Radiology, Pasterova 14, 11000 , Belgrade, Serbia

    Branka Kolundžija

Authors
  1. Ivan O. Juranić
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  2. Ana V. Tošić
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  3. Branka Kolundžija
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  4. Branko J. Drakulić
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Correspondence to Branko J. Drakulić.

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Juranić, I.O., Tošić, A.V., Kolundžija, B. et al. Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines. Mol Divers 18, 577–592 (2014). https://doi.org/10.1007/s11030-014-9528-4

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  • DOI: https://doi.org/10.1007/s11030-014-9528-4

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