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New prenylchalcones targeting the MDM2-p53 protein-protein interaction: synthesis and evaluation of antitumor activity
1 , 2 , 1 , 2 , 1, 3 , 1 , 1 , 1, 3 , * 1, 3
1  Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
2  LAQV/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
3  Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n 4450-208 Matosinhos, Portugal

Published: 31 October 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session ECMC-4

Among the chemical world of flavonoids, prenylated derivatives have been attracting the attention because of the myriad of their biological activities, with chalcones being widely reported for their antitumor activity against a variety of tumor cell lines [1]. In fact, it has been demonstrated that isoprenylation of flavonoids significantly increased their growth inhibitory effect on human tumor cell lines [2]. A series of prenylchalcones was synthesized and evaluated for the ability to inhibit the MDM2-p53 interaction using a yeast-based assay [3]. The capacity of all synthesized prenylchalcones and their non-prenylated precursors to inhibit the growth of human colon tumor HCT116 cells was evaluated and compared [3]. The overall results led to the identification of a hit compound, which behaved as potential inhibitor of the MDM2-p53 interaction in yeast, and showed improved cytotoxicity against human tumor cells expressing wild-type p53. In HCT116 cancer cells, it was also shown that the growth inhibitory effect of this prenylchalcone was associated with the induction of cell cycle arrest, and apoptosis.

  1. S. Venturelli et al. Nutrition, 2016, 32(11-12), 1171-1178.
  2. M.P. Neves et al. Chem. Biodivers., 2012, 9, 1133-1143.
  3. P. Brandão et al. Eur J Med Chem, 2018, 156, 711-721.

This research was partially supported by the Strategic Funding UID/Multi/04423/2013 and UID/MULTI/04378/2013 through national funds provided by FCT and ERDF, in the framework of the programme PT2020, the projects POCI-01-0145-FEDER-028736, PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599–PPCDT), PTDC/AAGTEC/0739/2014 (reference POCI-01-0145-FEDER-016793; Project 9471–PPCDT), and PTDC/DTPFTO/1981/2014 (reference POCl-01-0145-FEDER-016581), as well as by the project INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR), supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).

Keywords: Prenylated chalcones; MDM2-p53 inhibitors; antitumor activity
Comments on this paper
Maria Emília Sousa
Very promising compounds to look for new p53:MDM2 inhibitors, very nice presentation!

Carla Fernandes
Carla Fernandes
Very nice presentation and promising results!