A novel calix[4]pyrrole derivative as a potential anticancer agent that forms genotoxic adducts with DNA

Marta Geretto, Marco Ponassi, Martina Casale, Alessandra Pulliero, Grazia Cafeo, Ferdinando Malagreca, Aldo Profumo, Enrica Balza, Rakhmetkazhi Bersimbaev, Franz Heinrich Kohnke, Camillo Rosano, Alberto Izzotti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number11075
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

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