2. Academic Validation
  3. 4-(1,2-diarylbut-1-en-1-yl)isobutyranilide derivatives as inhibitors of topoisomerase II

4-(1,2-diarylbut-1-en-1-yl)isobutyranilide derivatives as inhibitors of topoisomerase II

  • Eur J Med Chem. 2016 Aug 8:118:79-89. doi: 10.1016/j.ejmech.2016.03.090.
Michael S Christodoulou 1,  Mikel Zarate 2,  Francesca Ricci 3,  Giovanna Damia 3,  Stefano Pieraccini 2,  Federico Dapiaggi 2,  Maurizio Sironi 2,  Leonardo Lo Presti 4,  Aída Nelly García-Argáez 5,  Lisa Dalla Via 6,  Daniele Passarella 2
Affiliations

Affiliations

  • 1 Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy. Electronic address: michalis.christ@gmail.com.
  • 2 Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy.
  • 3 Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
  • 4 Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, Italy; CNR-ISTM, Istituto di Scienze e Tecnologie Molecolari, Via Golgi 19, 20133 Milano, Italy; Center for Materials Crystallography, Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark.
  • 5 Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
  • 6 Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy. Electronic address: lisa.dallavia@unipd.it.
PMID: 27128175 DOI: 10.1016/j.ejmech.2016.03.090
Abstract

The synthesis and biological evaluation of a new library of 4-(1,2-diarylbut-1-en-1-yl)isobutyranilides is described. The new compounds were found to be cytotoxic in the micromolar range in two human tumor cell lines, MCF-7 (mammary gland adenocarcinoma) and HeLa (cervix adenocarcinoma) and two human ovarian Cancer cell lines (A2780 and OVCAR5). Detailed studies on the most active compound 6g show that it was able to induce Apoptosis and suggest Topoisomerase II as a possible intracellular target. The relevance of the interaction of the most active compound with Topoisomerase II is demonstrated and supported by docking studies.

Keywords

McMurry reaction; Tamoxifen derivatives; Topoisomerase I and II.

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