Naftoquinone derivatives: in vitro photo protective activity and interaction studies with tyrosinase and DNA

Melanoma is one of the most serious consequences of skin cancer where melanocytes proliferate actively with enhanced accumulation of melanin and tumor formation. The regu lation of the tyrosinase levei appear to contribute significantly to the enhanced synthesis and accumulation of melanin in melanocytes1. ln this way, the synthesis, characterization, in vitro studies of UVB sun protection factor, molecular docking with tyrosinase and initial DNA-ligand interaction studies of N-iminonaphthoquinones were carried out. The compounds were synthesized by nucleophilic addition reaction to the C1 or C2 carbonyl carbon of the 1,4-naphthoquinone by the nitrogenated reagent2. The UVB sun protection factor (SPF-UVB) was determined using the Mansur et ai. procedure2 , in which ali the molecules tested presented SPF > 7 with relevant photoprotective activity. Lapachol N-imino (1) derivatives exhibited the highest SPF-UVB when compareci with oxybenzophenone3 . Nimino naphthoquinone (2) analogues demonstrate that the exchange of carbonyl by a nitrogen group potentiated the photoprotective activity in six-fold compareci with starting quinone. The theoretical studies of the tyrosinase interaction with the most effective photo protector compounds showed that 1 had higher binding affinity (-8.0 kcal mol-1), followed by 3 and 2 (-6.9 and -6.5 kcal mol-1) , respectively. These results have the sarne trend of the experimental data. However, in this first evaluation these compounds would be noncompetitive inhibitors. Finally, in the competition assays with Hoechst probe 1 has interacted with DNA via groove, which may in future be exploited exploring DNA as a therapeutic target.