Thymidine Phosphorylase Inhibitory Potential and Molecular Docking Studies of Secondary Metabolites Isolated From <i>Fernandoa adenophylla</i> (Wall. ex G. Don) Steenis

This study investigates the potential of Fernandoa adenophylla, a South American plant, as a reservoir of compounds with thymidine phosphorylase (TP) inhibitory activity. Through a comprehensive approach combining in vitro assays and molecular docking analysis, we isolated and characterized bioactive compounds from F. adenophylla, including lapachol, alpha-lapachone, Peshawaraquinone, dehydro-α-lapachone, and indanone derivative (Methyl-1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1carboxylate). Our results reveal substantial TP inhibition by these compounds, with Lapachol (1) and Indanone derivative (5) demonstrating notable potency, exhibiting IC₅₀ values of 2.3 ± 0.1 and 1.8 ± 0.5 µM, respectively. Molecular docking analysis supported experimental in-vitro results, revealing strong binding affinities of the tested compounds toward both human TP and Escherichia coli TP, with the indanone derivatives exhibiting the most favorable binding energies (-7.50 and -7.80 kcal/mol, respectively). Key interactions with important catalytic residues were identified, highlighting these natural products' structural complementarity and binding stability. These docking results correlate well with the observed in vitro inhibitory activities, reinforcing the compounds' therapeutic relevance. This study underscores the therapeutic potential of F. adenophylla-derived compounds as effective TP inhibitors, highlighting the significance of natural products in drug discovery.