The Acid/Base Characterization of Molecules with Epigenetic Activity.

The acidic and basic functional groups in a molecule strongly influence its physicochemical properties, affinity for a macromolecule, pharmacokinetics, and toxicity. For instance, basicity has been correlated with molecular promiscuity, hERG blockade, and phospholipidosis. Nonetheless, a systematic characterization of the acid/base profile of epigenomic databases has not been reported. The present study describes an analysis of the acidic ionization constants distribution of a library of 7820 compounds with reported activity against epigenetic targets. Furthermore, the epigenomics database's acid/base profile is compared to the reference libraries of food chemicals, natural products, and approved drugs. It was found that the acid/base profile of histone lysine demethylase ligands is more similar to previously approved drugs, and histone acetyltransferase ligands have acidic and basic functional groups largely found in food chemicals and natural products, which support the potential of these libraries for finding new epigenetic inhibitors.