2. Academic Validation
  3. Discovery of a pyrimidine compound endowed with antitumor activity

Discovery of a pyrimidine compound endowed with antitumor activity

  • Invest New Drugs. 2020 Feb;38(1):39-49. doi: 10.1007/s10637-019-00762-y.
Ludovica Taglieri 1,  Francesco Saccoliti 2,  Alice Nicolai 1 3,  Giovanna Peruzzi 4,  Valentina Noemi Madia 2,  Valeria Tudino 2,  Antonella Messore 2,  Roberto Di Santo 2,  Marco Artico 3,  Samanta Taurone 3,  Maurizio Salvati 5,  Roberta Costi 6,  Susanna Scarpa 1
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy.
  • 2 Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy.
  • 3 Department of Sensory Organs, Sapienza University, Viale del Policlinico 155, 00161, Rome, Italy.
  • 4 Italian Institute of Technology, Center for Life Nanoscience@Sapienza, Viale Regina Elena 324, 00161, Rome, Italy.
  • 5 Department of Human Neurosciences, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy.
  • 6 Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. roberta.costi@uniroma1.it.
PMID: 30900116 DOI: 10.1007/s10637-019-00762-y
Abstract

Recently, some synthetic nitrogen-based heterocyclic molecules, such as PJ34, have shown pronounced antitumor activity. Therefore, we designed and synthesized new derivatives characterized by a nitrogen-containing scaffold and evaluated their antiproliferative properties in tumor cells. We herein report the effects of three newly synthesized compounds on cell lines from three different human cancers: triple-negative breast Cancer, colon carcinoma and glioblastoma. We found that two of these compounds did not affect proliferation, while the third significantly inhibited replication of the three cell lines. Moreover, this third molecule at 20 μM led to the upregulation of p21 and p27 and blockage of the cell cycle at G0/G1; in addition, it induced Apoptosis in all three cell lines when used at higher concentrations (30-50 μM). The results demonstrate that this compound is a potent inhibitor of replication, an inducer of Apoptosis and a negative regulator of cell cycle progression for Cancer cells of different histotypes. Our data suggest a potential role for this new molecule as an interesting and powerful tool for new approaches in treating various cancers.

Keywords

Breast cancer; Colon carcinoma; Glioblastoma multiforme; PJ34; Phenathridinone; Pyrimidine.

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