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Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety

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Abstract

A series of new hybrid molecules with a hydrazone fragment were synthesized and characterized by Fourier transform-infrared spectroscopy, nuclear magnetic resonance, mass spectrometry, and elemental analysis. The nuclear magnetic resonance spectra of the hydrazones 4a–c showed exchange of syn and antiperiplanar conformers around the amide bond, the more stable being the antiperiplanar one. The nuclear Overhauser effect spectroscopy (NOESY) spectra confirm E configuration around C=N bond. The tested compounds exhibited concentration-dependent cytotoxic effects against human tumor cell lines in a micromolar range (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay). Hydrazone 4a proved to be the most potent antiproliferative agent of the series. Within the antioxidant screening 8b exhibited the highest radical scavenging activity (% RSA max) and the largest rate constant for the reaction with 2,2-diphenyl-1-picrylhydrazyl.

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Acknowledgments

Dedicated to Professor Ivan G. Pojarlieff on the occasion of his 80th birthday. This study was supported by the National Research Fund of Bulgaria (projects UNA-17/2005 and DRNF-02/13/2009) and by the Ministry of Education, Science and Technological Development of Republic of Serbia (Project No. III41018). We appreciate greatly the help with mass spectroscopy of V. Arabadjiev.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Pharmacy, Medical University, 1000, Sofia, Bulgaria

    Violina T. Angelova & Boryana Nikolova-Mladenova

  2. Laboratory of Nuclear Magnetic Resonance, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Nikolay G. Vassilev

  3. Faculty of Technology, Department of Applied and Engineering Chemistry, University of Novi Sad, Novi Sad, Serbia

    Jasmina Vitas & Radomir Malbaša

  4. Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University, 1000, Sofia, Bulgaria

    Georgi Momekov

  5. Department of Toxicology, Faculty of Pharmacy, University of Belgrade, 11221, Belgrade, Serbia

    Mirjana Djukic

  6. Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, Italy

    Luciano Saso

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  1. Violina T. Angelova
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Correspondence to Violina T. Angelova.

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Angelova, V.T., Vassilev, N.G., Nikolova-Mladenova, B. et al. Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety. Med Chem Res 25, 2082–2092 (2016). https://doi.org/10.1007/s00044-016-1661-4

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