TY - JOUR
T1 - A novel calix[4]pyrrole derivative as a potential anticancer agent that forms genotoxic adducts with DNA
AU - Geretto, Marta
AU - Ponassi, Marco
AU - Casale, Martina
AU - Pulliero, Alessandra
AU - Cafeo, Grazia
AU - Malagreca, Ferdinando
AU - Profumo, Aldo
AU - Balza, Enrica
AU - Bersimbaev, Rakhmetkazhi
AU - Kohnke, Franz Heinrich
AU - Rosano, Camillo
AU - Izzotti, Alberto
PY - 2018/12/1
Y1 - 2018/12/1
N2 - meso-(p-acetamidophenyl)-calix[4]pyrrole 3 was found to exhibit remarkable cytotoxicity towards A549 cancer cells. A comparative study including the isomer of 3meso-(m-acetamidophenyl)-calix[4]pyrrole 5, as well as molecules containing ‘fragments’ of these structures, demonstrated that both the calix[4]pyrrole and the acetamidophenyl units are essential for high cytotoxicity. Although calix[4]pyrroles and other anion-complexing ionophores have recently been reported to induce apoptosis by perturbing cellular chloride concentrations, in our study an alternative mechanism has emerged, as proven by the isolation of covalent DNA adducts revealed by the 32P postlabelling technique. Preliminary pharmacokinetic studies indicate that 3 is able to cross the Blood-Brain-Barrier, therefore being a potential drug that could kill primary and brain metastatic cancer cells simultaneously.
AB - meso-(p-acetamidophenyl)-calix[4]pyrrole 3 was found to exhibit remarkable cytotoxicity towards A549 cancer cells. A comparative study including the isomer of 3meso-(m-acetamidophenyl)-calix[4]pyrrole 5, as well as molecules containing ‘fragments’ of these structures, demonstrated that both the calix[4]pyrrole and the acetamidophenyl units are essential for high cytotoxicity. Although calix[4]pyrroles and other anion-complexing ionophores have recently been reported to induce apoptosis by perturbing cellular chloride concentrations, in our study an alternative mechanism has emerged, as proven by the isolation of covalent DNA adducts revealed by the 32P postlabelling technique. Preliminary pharmacokinetic studies indicate that 3 is able to cross the Blood-Brain-Barrier, therefore being a potential drug that could kill primary and brain metastatic cancer cells simultaneously.
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UR - http://www.scopus.com/inward/citedby.url?scp=85050636430&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-29314-9
DO - 10.1038/s41598-018-29314-9
M3 - Article
AN - SCOPUS:85050636430
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11075
ER -