Bioinspired oxidation in the CYP of isomers orientin and isoorientin using Salen complexes

RATIONALE: Orientin and isoorientin are C-glycosidic flavonoids, considered as markers of some plant species as Passiflora edulis var. flavicarpa Degener and reported in the literature to have pharmacological properties. In order to evaluate and characterize the in vitro metabolism of flavonoids, phase I biotransformation reactions were simulated using Salen complexes. METHODS: These flavonoids were oxidized separately in biomimetic reaction in different proportions, using one oxidant, m-chloroperbenzoic acid (m-CPBA) or iodozylbenzen (PhIO), and one catalyst, the Jacobsen catalyst or [Mn(3-MeOSalen)Cl]. The [Mn(3-MeOSalen)Cl] was synthesized and characterized by spectrometric techniques. The oxidation potentials of the catalysts were compared. All reactions were monitored and analyzed by UPLC-DAD and HPLC/MS/MS. RESULTS: The analysis by UPLC-DAD and HPLC/MS/MS showed that isoorientin produces more products than orientin and that the [Mn(3-MeOSalen)CI] produces more products than the Jacobsen catalyst. In addition, the [Mn(3-MeOSalen)CI] catalyst, which has a higher oxidation potential, formed products with an addition of one or two atoms of oxygen, while the Jacobsen catalyst formed compounds with only one added oxygen atom. The products with the addition of one oxygen were mainly epoxides, while those with two added oxygens formed an epoxide in the C-ring and incorporated the other oxygen into the glycosidic moiety. CONCLUSIONS: The formation of epoxides is common in biomimetic reactions and they may represent a safety risk in medicinal products due to their high reactivity. This study may serve as a basis for subsequent pharmacological and toxicological studies that investigate the presence of these compounds as phase I metabolites, and ensure the safe use of plant products containing orientin as a chemical marker.