Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors.

Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site.