Oxime Functionalization of Naringin and Naringenin: Tuning Structural, Physicochemical, and Biological Profiling.

Oxime functionalization represents a promising strategy for modulating the physicochemical and biological properties of flavonoids, with the relationship to biological behavior remaining ill-defined. In this work, naringin and naringenin have been converted to their oximated derivatives through an optimized high-yield synthetic protocol. Both derivatives were characterized by elemental analysis, FT-IR, UV-Visible, NMR, ESI-MS, and, for the first time, X-ray crystallography. Spectroscopic analyses confirmed the transformation of the carbonyl group to oxime (C = N-OH) and revealed the presence of E/Z oxime isomers, while crystallographic analysis demonstrated the participation of the oxime group in hydrogen-bonding interactions in the crystal lattice. Oxime modification altered their electronic structure and solid-state fluorescence properties. Naringin-oxime exhibited improved solubility in biological media and was further evaluated biologically. It exhibited concentration- and tissue-dependent protective effects against H2O2-induced oxidative stress, under pre/post-treatment conditions, in neuronal cell models, and antibacterial activity against Gram-(+) and Gram(-) bacteria. Complementary molecular docking studies provided insights into potential ligand-protein interactions with antioxidant- and antibacterial-related targets, thereby supporting the experimental observations. Collectively, the formulated structure-property-activity profile renders oximation a significant strategy for tuning flavonoid physicochemical and biological properties, thus highlighting flavonoid-oximes as multifunctional antibacterial and neuroprotective candidates.