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  3. Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines

Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines

  • Eur J Med Chem. 2016 Jul 19:117:1-7. doi: 10.1016/j.ejmech.2016.04.006.
G Bertuzzi 1,  E Locatelli 1,  D Colecchia 2,  P Calandro 3,  B F Bonini 1,  J Z Chandanshive 1,  A Mazzanti 1,  P Zani 1,  M Chiariello 2,  M Comes Franchini 4
Affiliations

Affiliations

  • 1 Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy.
  • 2 Istituto di Fisiologia Clinica (IFC), Consiglio Nazionale delle Ricerche (CNR), Siena, Italy; IstitutoToscanoTumori (ITT), Core Research Laboratory (CRL), AOU Senese, Italy.
  • 3 IstitutoToscanoTumori (ITT), Core Research Laboratory (CRL), AOU Senese, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Italy.
  • 4 Department of Industrial Chemistry "Toso Montanari", University of Bologna, Viale Risorgimento, 40136, Bologna, Italy. Electronic address: mauro.comesfranchini@unibo.it.
PMID: 27081742 DOI: 10.1016/j.ejmech.2016.04.006
Abstract

In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,β-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent Anticancer capability: in vitro cytotoxicity test on five different Cancer cell lines showed interesting IC50 values in the range of 15-60 μM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited Anticancer compounds, such as 5-FU and NVP-BEZ235.

Keywords

1,3-Dipolar cycloaddition; Anticancer drug; Lactam; Pyrazole.

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