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Lewis acid-induced intramolecular access to novel steroidal ring D-condensed arylpyrazolines exerting in vitro cell-growth-inhibitory effects

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Abstract

Novel androstenoarylpyrazolines were synthesized stereoselectively by the \(\hbox {BF}_{3}\)-induced intramolecular 1,3-dipolar cycloaddition of alkenyl hydrazones obtained from a steroidal D-seco-aldehyde with differently substituted arylhydrazines. The reaction rates were observed to be affected significantly by the electronic character of the substituents on the aromatic moiety. The cyclizations are assumed to follow a stepwise rather than a pure concerted mechanism, to afford arylpyrazolidines as primary products. Spontaneous oxidation of the saturated \(N\),\(N\)-heterocycles under the reaction conditions led to pyrazoline derivatives in good to excellent yields. In in vitro antiproliferative studies on a panel of breast cancer cells (MCF7, T47D, MDA-MB-231, and MDA-MB-361), some of the 3-deacetylated cycloadducts exerted marked growth inhibitory activities, with \(\hbox {IC}_{50}\) values in the range 3.56–9.32 \(\upmu \hbox {M}\), which are comparable to that for the reference agent cisplatin.

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Acknowledgments

Financial support by the Hungarian Scientific Research Fund (OTKA K-109107, OTKA K-109293) is gratefully acknowledged. The research by G. Mótyán was supported by the European Union and The State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP 4.2.4. A/2-11/1-2012-0001 “National Excellence Program”.

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Authors and Affiliations

  1. Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary

    Gergő Mótyán, Gyula Schneider, János Wölfling & Éva Frank

  2. Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, Szeged, 6720, Hungary

    István Zupkó & Renáta Minorics

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  1. Gergő Mótyán
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  2. István Zupkó
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  3. Renáta Minorics
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  4. Gyula Schneider
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  5. János Wölfling
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Correspondence to Éva Frank.

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Dedicated to Professor Irén Vincze on the occasion of her 85th birthday.

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Mótyán, G., Zupkó, I., Minorics, R. et al. Lewis acid-induced intramolecular access to novel steroidal ring D-condensed arylpyrazolines exerting in vitro cell-growth-inhibitory effects. Mol Divers 19, 511–527 (2015). https://doi.org/10.1007/s11030-015-9593-3

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