Tetrazole as a Replacement of the Electrophilic Group in Characteristic Prolyl Oligopeptidase Inhibitors.

4-Phenylbutanoyl-aminoacyl-2()-tetrazolylpyrrolidines were studied as prolyl oligopeptidase inhibitors. The compounds were more potent than expected from the assumption that the tetrazole would also here be a bioisostere of the carboxylic acid group and the corresponding carboxylic acids are at their best only weak inhibitors. The aminoacyl groups l-prolyl and l-alanyl gave potent inhibitors with IC values of 12 and 129 nM, respectively.

Quercetin based derivatives as sirtuin inhibitors.

Polyphenols synthesized by plants and fungi have various pharmacological effects. The ability of polyphenols to modulate sirtuins has gained considerable interest due to the role of sirtuins in aging, insulin sensitivity, lipid metabolism, inflammation, and cancer. In particular, sirtuin 6 (SIRT6) has gained importance in regulating a variety of cellular processes, including genomic stability and glucose metabolism.

Natural polyphenols as sirtuin 6 modulators.

Flavonoids are polyphenolic secondary metabolites synthesized by plants and fungus with various pharmacological effects. Due to their plethora of biological activities, they have been studied extensively in drug development. They have been shown to modulate the activity of a NAD-dependent histone deacetylase, SIRT6.