Design, CTAB-catalyzed ultrasound-assisted synthesis and tyrosinase inhibition potential of naphthofuran-triazole conjugates

Abstract

The development of novel and efficient tyrosinase inhibitors is a critical necessity of agricultural, cosmetic and medicinal chemistry. Bearing in mind the therapeutical potential of naphthofuran-containing organic compounds, we carried out the CTAB-catalyzed ultrasound-assisted synthesis of a library of novel naphthofuran-triazole joined N-aryl/alkyl acetamides 20(a–j) in 74–92% yield, which were further assessed for their tyrosinase inhibitory potential by taking kojic acid and ascorbic acid as standard inhibitors. The tyrosinase inhibitory assay demonstrated the promising tyrosinase inhibiting tendency of all prepared derivatives 20(a–h) as they all were found to be more efficient in comparison to the standard kojic acid. Similarly, most of the derivatives also exhibited tyrosinase inhibition potency in juxtaposition to ascorbic acid. More specifically, among the catalog of compounds, 20f and 20i exhibited potent inhibition results with IC₅₀ = 0.51 ± 0.12 and 1.99 ± 0.07, respectively. Overall, 20f was shown to be the most efficacious tyrosinase inhibitor, owing to the presence of an electronegative group, i.e., 2-chloro substitution on the phenyl ring. The tyrosinase inhibition activity results of 20f and 20i were further supplemented with molecular docking analysis to validate experimental studies. In silico modelling findings revealed their significant interactions with the tyrosinase protein (PDB ID: 5OAE), thereby illustrating the efficient docking score of −7.10 kcal mol⁻¹ and −6.95 kcal mol⁻¹ in comparison to kojic acid (−5.03 kcal mol⁻¹).