Elisabetta Di Bello, Veronica Sian, Giulio Bontempi, Clemens Zwergel, Rossella Fioravanti, Beatrice Noce, Carola Castiello, Stefano Tomassi, Davide Corinti, Daniela Passeri, Roberto Pellicciari, Ciro Mercurio, Mario Varasi, Lucia Altucci, Marco Tripodi, Raffaele Strippoli, Angela Nebbioso, Sergio Valente, Antonello Mai
After over 30 years of research, the development of HDAC inhibitors led to five FDA/Chinese FDA-approved drugs and many others under clinical or preclinical investigation to treat cancer and non-cancer diseases. Herein, based on our recent development of pyridine-based isomers as HDAC inhibitors, we report a series of novel 5-acylamino-2-pyridylacrylic- and -picolinic hydroxamates and 2'-aminoanilides 5-8 as anticancer agents. The hydroxamate 5d proved to be quite HDAC3/6-selective exhibiting IC50 values of 80 and 11 nM, respectively, whereas the congener 5e behaved as inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) at nanomolar level...
December 15, 2022: European Journal of Medicinal Chemistry