Exploring Hippuric Acid’s Putative Protective Role in Aging through In Silico and In Vitro Screening

To investigate mechanisms underlying its protective role, <i>in silico</i> screening of large bioactivity data sets was performed and integrated with results from <i>in vitro</i> assays. A multifingerprint similarity approach was employed to identify close HA analogues and their reported targets.

HA analogues were identified with reported potencies in the low-micromolar or nanomolar range toward transporters (solute carriers, organic anion transporters, multidrug resistance-associated proteins), epigenetic regulators (histone deacetylases), and enzymes linked to inflammation, proteostasis, or vascular homeostasis (carbonic anhydrases, cyclooxygenase-2, soluble epoxide hydrolase, neprilysin). Additional evidence pointed to proteins involved in detoxification, energy metabolism, and neurodegeneration (kynureninase, microtubule-associated protein tau, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase), supporting their plausibility as candidate HA targets.