TY - JOUR
T1 - N-thioalkylcarbazoles derivatives as new anti-proliferative agents
T2 - synthesis, characterisation and molecular mechanism evaluation
AU - Sinicropi, Maria Stefania
AU - Iacopetta, Domenico
AU - Rosano, Camillo
AU - Randino, Rosario
AU - Caruso, Anna
AU - Saturnino, Carmela
AU - Muià, Noemi
AU - Ceramella, Jessica
AU - Puoci, Francesco
AU - Rodriquez, Manuela
AU - Longo, Pasquale
AU - Plutino, Maria Rosaria
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - apoptosis
KW - Carbazole derivatives
KW - caspases
KW - immunofluorescence
KW - topoisomerase II
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U2 - 10.1080/14756366.2017.1419216
DO - 10.1080/14756366.2017.1419216
M3 - Article
C2 - 29383954
AN - SCOPUS:85041561786
VL - 33
SP - 434
EP - 444
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
SN - 1475-6366
IS - 1
ER -