In silico identification and in vitro activity of natural products as ADP-ribosyl transferase member 8 inhibitors

Aim: ADP-ribosyl transferase member 8 (ARTD8) of the ARTD superfamily has been identified as a possible anti-cancer, antiviral and anti-inflammatory target. 

Method: Pure actives from natural products with a documented anti-cancer activity were docked into the catalytic site of 3SMI.pdb using PyRx and AutoDock Vina. 

Results: Epigallocatechin gallate (EGCG), trans-resveratrol, indol-3-carbinol, curcumin, quercetin and naringenin were investigated, in vitro, against ARTD8, revealing EGCG and quercetin as lead compounds, with EGCG displaying complete inhibition at 10 μM. Both EGCG and quercetins docked poses spanned across both the nicotinamide and adenine subsites of the catalytic domain, interacting with conserved residues Ser1641 and/or Ser1607 and Tyr1646. Thereby, suggesting that the meta-hydroxy group on the catechin ring B backbone may be responsible for these inhibition effects.