2. Academic Validation
  3. Synthesis and antiproliferative activity of novel selenoester derivatives

Synthesis and antiproliferative activity of novel selenoester derivatives

  • Eur J Med Chem. 2014 Feb 12:73:153-66. doi: 10.1016/j.ejmech.2013.11.034.
Enrique Domínguez-Álvarez 1,  Daniel Plano 2,  María Font 3,  Alfonso Calvo 4,  Celia Prior 4,  Claus Jacob 5,  Juan Antonio Palop 6,  Carmen Sanmartín 2
Affiliations

Affiliations

  • 1 Synthesis Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus, 66123 Saarbruecken, Germany.
  • 2 Synthesis Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
  • 3 Molecular Modeling Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
  • 4 Oncology Division, Center for Applied Medical Research, CIMA, University of Navarra, Pío XII 53, E-31008 Pamplona, Spain.
  • 5 Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus, 66123 Saarbruecken, Germany.
  • 6 Synthesis Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain. Electronic address: jpalop@unav.es.
PMID: 24389510 DOI: 10.1016/j.ejmech.2013.11.034
Abstract

A series of 31 new selenoesters were synthesized and their cytotoxic activity was evaluated against a prostate Cancer cell line (PC-3). The most active compounds were also tested against three tumoural cell lines (MCF-7, A-549 and HT-29) and one non-tumour prostate cell line (RWPE-1). Thirteen compounds showed significant activity towards all tumour cells investigated, and some of them were even more potent than etoposide and cisplatin, which were used as reference drugs. Because of their pronounced potency and/or selectivity, four analogues (5, 21, 28 and 30), were selected in order to assess their redox properties related to a possible redox modulating activity. The Glutathione Peroxidase (GPx) assay showed slight activity for compound 30 and the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) assay showed a weak activity for compounds 5 and 28. The present results revealed that analogues 5, 21, 28 and 30 might serve as a useful starting point for the design of improved anti-tumour agents.

Keywords

Antiproliferatives; Cancer; Cytotoxicity; Selenium.

Figures