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Cyanogenic Glycosides
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
During plant growth, amino acids not required for protein synthesis are metabolized into α-hydroxynitriles and then cyanogenic glycosides, which are stored in the cell vacuoles. This effectively segregates canogenic glycosides spatially from endogenous hydrolyzing enzymes (e.g., β-1,6-glucosidases and hydroxynitrile lyases) in the cell cytosol (or the cell wall and laticifers as in the case of cassava linamarase), preventing canogenic glycoside-related autotoxicity. Additionally, cyanide from cyanogenic glycoside (e.g., cyanogen linamarin) may be converted by β-cyanoalanine synthase into cyanoalanine plus hydrogen sulfide in the presence of cysteine, and cyanoalanine is then converted by nitrilase to asparagine. This also helps limit the potential self-damage by cyanogenic glycosides.
Interaction of letrozole and its degradation products with aromatase: chemometric assessment of kinetics and structure-based binding validation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Michele De Luca, Maria Antonietta Occhiuzzi, Bruno Rizzuti, Giuseppina Ioele, Gaetano Ragno, Antonio Garofalo, Fedora Grande
In this work, we describe in detail the degradation profile of LTZ under different experimental conditions. It is well known that nitrile catabolism can follow two distinct pathways: (1) conversion to carboxylic acid catalysed by nitrilase, and (2) amide formation mediated by nitrile hydratase/amidase. These reactions can be easily reproduced using different hydrolytic chemical conditions14. A further factor leading to LTZ degradation is represented by non-hydrolytic oxidative conditions, when an easy formation of the corresponding 1-(bis(4-cyanophenyl)methyl)-1H-1,2,4-triazole-2-oxide (LNO) is observed. The formation of other minor degradation products has been reported6, but their presence has not been considered here. This study aimed to define the kinetics of the degradation products of LTZ, monitoring them by UV/Vis spectrophotometry and processing the spectral data by Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) methodology. This chemometric procedure was used because it is particularly effective in following the chemical transformation processes, allowing to resolve the spectra and concentration profiles of the components involved. An independent HPLC-DAD method was defined to validate the results obtained by the multivariate resolution of the UV kinetic studies. The UV spectra from the HPLC-DAD detector were compared with the spectra predicted by the multivariate procedure, demonstrating a significant overlap of the spectral curves related to the degradation products. Furthermore, docking experiments were performed to verify whether the degradation compounds were able to accommodate in the aromatase active site with binding mode conformation and affinity comparable to the parent drug. To this aim, LTZ and its three main degradation compounds were docked in the crystal structure of aromatase and the results were compared with those obtained for androstenedione (ASD), the endogenous ligand of the enzyme.