N-thioalkylcarbazoles derivatives as new anti-proliferative agents: synthesis, characterisation and molecular mechanism evaluation

Maria Stefania Sinicropi, Domenico Iacopetta, Camillo Rosano, Rosario Randino, Anna Caruso, Carmela Saturnino, Noemi Muià, Jessica Ceramella, Francesco Puoci, Manuela Rodriquez, Pasquale Longo, Maria Rosaria Plutino

Research output: Contribution to journalArticlepeer-review

Abstract

Synthetic or natural carbazole derivatives constitute an interesting class of heterocycles, which showed several pharmaceutical properties and occupied a promising place as antitumour tools in preclinical studies. They target several cellular key-points, e.g. DNA and Topoisomerases I and II. The most studied representative, i.e. Ellipticine, was introduced in the treatment of metastatic breast cancer. However, because of the onset of dramatic side effects, its use was almost dismissed. Many efforts were made in order to design and synthesise new carbazole derivatives with good activity and reduced side effects. The major goal of the present study was to synthesise a series of new N-thioalkylcarbazole derivatives with anti-proliferative effects. Two compounds, 5a and 5c, possess an interesting anti-proliferative activity against breast and uterine cancer cell lines without affecting non-tumoural cell lines viability. The most active compound (5c) induces cancer cells death triggering the intrinsic apoptotic pathway by inhibition of Topoisomerase II.

Original languageEnglish
Pages (from-to)434-444
Number of pages11
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • apoptosis
  • Carbazole derivatives
  • caspases
  • immunofluorescence
  • topoisomerase II

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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