In vitro and in silico investigation of Daturaolone as a novel aldose reductase, thymidine phosphorylase inhibitor from Datura metel Linnaeus

Résumé fourni par la source

Natural products have consistently been a prolific source of bioactive compounds, with traditional medicinal plants providing valuable leads for drug discovery. In this study, a novel amyrin-type triterpenoid, daturaolone, was isolated from the chloroform fraction of the fruits of D. metel. The compound was structurally characterized using advanced spectroscopic techniques. Integrated computational analyses, including molecular docking, ADME–toxicity profiling, and PASS analysis, were employed to provide supportive mechanistic and pharmacokinetic insights. Biological activity assessment revealed that daturaolone exhibits inhibitory effects against aldose reductase (AKR1B1) and thymidine phosphorylase (TYMP), with IC₅₀ values of 1.31 ± 0.03 µM and 18.98 ± 0.58 µM, respectively. These findings suggest potential relevance for modulating metabolic and angiogenesis-associated enzymatic pathways, particularly through the inhibition of aldose reductase involved in the polyol pathway and thymidine phosphorylase linked to nucleotide metabolism. ADME and toxicity assessments suggested that daturaolone possesses a generally favorable drug-likeness profile, with no major predicted pharmacokinetic liabilities and a low predicted toxicity risk (ProTox Class 6), supporting its suitability for further investigation. Molecular docking analyses provided a structural rationale for enzyme inhibition, indicating favorable binding of daturaolone within the catalytic pockets of both AKR1B1 and TYMP, with binding trends qualitatively consistent with experimental inhibition data. PASS analysis suggested chemopreventive, anti-inflammatory, oxidoreductase-inhibitory, and insulin-modulating activities, indicating a broader predicted pharmacological spectrum. Collectively, these findings underline the promising bioactivity of daturaolone and provide a foundation for further pharmacological and mechanistic studies.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.