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Synthesis, structure, and in vitro anticancer activity of new polycyclic 1,2-diazines

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Abstract

The synthesis, structure, and in vitro anticancer activity of a new class of anticancer derivatives with dihydrobenzo[5,6]isoindolo[1,2-a]phthalazine and dihydrobenzo[f]pyridazino[6,1-a]isoindole skeletons are presented. The preparation is straight and efficient, involving two steps only: a N-alkylation of the pyridazine or phthalazine heterocycle, followed by a [3 + 2] dipolar cycloaddition of 1,2-diazinium ylides to the corresponding dipolarophiles. The synthesis was performed under microwave and ultrasound (US) irradiation as well as under conventional thermal heating. The most effective conditions in term of yields and time were found to be US irradiation. The penta- and tetra-cyclic 1,2-diazines were evaluated for their in vitro anticancer activity. The pentacyclic 1,2-diazine derivatives exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM, and Breast Cancer MCF7. A feasible explanation for anticancer efficiency of the pentacyclic 1,2-diazines have been furnished, being correlated with the mechanisms of action.

Graphical Abstract

The synthesis (conventional thermal heating, microwave and ultrasound irradiation), structure, and in vitro anticancer activity of a new class of anticancer molecules with polycyclic 1,2-diazines skeleton is presented.

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Acknowledgments

Authors are thankful to POSDRU Grant 89/1.5/S/49944, “Developing the innovation capacity and improving the impact of research through post-doctoral programs,” for financial support.

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Authors and Affiliations

  1. Department of Organic and Biochemistry, “Al. I. Cuza” University of Iasi, Bd. Carol 11, 700506, Iasi, Romania

    Dorina Mantu, Dan Maftei & Vasilichia Bejan

  2. Biological Research Institute, Bd. Carol 20A, Iasi, Romania

    Dorina Iurea

  3. Faculty of Dentistry, “Apollonia” University of Iasi, Str. Păcurari 11, 700511, Iasi, Romania

    Cornelia Ursu

Authors
  1. Dorina Mantu
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  2. Dan Maftei
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  3. Dorina Iurea
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  4. Cornelia Ursu
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  5. Vasilichia Bejan
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Corresponding author

Correspondence to Vasilichia Bejan.

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44_2013_878_MOESM1_ESM.doc

The NMR spectra (1H NMR, 13C NMR, 2D-COSY, 2D-HETCOR (HMQC), and long-range 2D-HETCOR (HMBC)) for compounds (5b) and (6b). (DOC 1896 kb)

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Mantu, D., Maftei, D., Iurea, D. et al. Synthesis, structure, and in vitro anticancer activity of new polycyclic 1,2-diazines. Med Chem Res 23, 2909–2915 (2014). https://doi.org/10.1007/s00044-013-0878-8

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  • DOI: https://doi.org/10.1007/s00044-013-0878-8

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