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

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 mos...

Full description

Saved in:
Bibliographic Details
Published inJournal of enzyme inhibition and medicinal chemistry Vol. 33; no. 1; pp. 434 - 444
Main Authors Sinicropi, Maria Stefania, Iacopetta, Domenico, Rosano, Camillo, Randino, Rosario, Caruso, Anna, Saturnino, Carmela, Muià, Noemi, Ceramella, Jessica, Puoci, Francesco, Rodriquez, Manuela, Longo, Pasquale, Plutino, Maria Rosaria
Format Journal Article
LanguageEnglish
Published ABINGDON Taylor & Francis 01.01.2018
Taylor & Francis Group
Subjects
apoptosis
Biochemistry & Molecular Biology
Carbazole derivatives
caspases
Chemistry, Medicinal
immunofluorescence
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Research Paper
Science & Technology
topoisomerase II
POLY(ADP-RIBOSE) POLYMERASE
CELLS
Carbazole derivatives
apoptosis
CYTOTOXIC ACTIVITY
ELLIPTICINES
topoisomerase II
INHIBITION
DNA
BIOLOGICAL EVALUATION
CANCER STATISTICS
caspases
immunofluorescence
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:These authors contributed equally to this work.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2017.1419216