Francesco Fiorentino, Emanuele Fabbrizi, Alessia Raucci, Beatrice Noce, Rossella Fioravanti, Sergio Valente, Chantal Paolini, Ruggero De Maria, Christian Steinkühler, Paola Gallinari, Dante Rotili, Antonello Mai
Cancer stem cells (CSCs) are a niche of highly tumorigenic cells featuring self-renewal, activation of pluripotency genes, multidrug resistance, and ability to cause cancer relapse. Seven HDACi (1-7), showing either hydroxamate or 2'-aminoanilide function, were tested in colorectal cancer (CRC) and glioblastoma multiforme (GBM) CSCs to determine their effects on cell proliferation, H3 acetylation levels and in-cell HDAC activity. Two uracil-based hydroxamates, 5 and 6, which differ in substitution at C5 and C6 positions of the pyrimidine ring, exhibited the greatest cytotoxicity in GBM (5) and CRC (6) CSCs, followed by the pyridine-hydroxamate 2, with 2- to 6-fold higher potency than the positive control SAHA...
March 26, 2024: ChemMedChem