Novel 1,4-Dihydropyridines as Specific Binders and Activators of SIRT3 Impair Cell Viability and Clonogenicity and Downregulate Hypoxia-Induced Targets in Cancer Cells.

The mitochondrial SIRT3 modulates several biological pathways such as cancer, metabolism, and hypoxia-related diseases. Recently, we discovered new 1,4-dihydropyridines, compounds and , the latter being a SIRT3-specific activator. In the present work, a novel - and -related small series of compounds have been developed, with displaying the strongest SIRT3 binding and activation, with a of 29 μM and 387% of enzyme activation.