Miglitol

Diabetes mellitus, characterized by persistent hyperglycemia, remains a critical global health challenge. Inhibition of human pancreatic alpha-amylase, a key enzyme catalyzing carbohydrate digestion, is a promising approach to manage postprandial glucose levels. Cinnamomum zeylanicum, a medicinal plant known for its therapeutic potential, harbors bioactive compounds that can act as natural alpha-amylase inhibitors, though their mechanisms remain underexplored. In this study, molecular docking and 200 ns molecular dynamics (MD) simulations were employed to evaluate the inhibitory potential of 18 phytochemicals derived from Cinnamomum zeylanicum. Two lead compounds, 1HE (1,2,4a,5,6,8a-Hexahydro-1-isopropyl-4,7-dimethylnaphthalene) and C4B (cis-4-Benzyl-2,6-diphenyl-tetrahydropyran), exhibited superior binding affinities (-7.91 and -8.78 kcal/mol, respectively) compared to the FDA-approved inhibitors, acarbose (-8.2 kcal/mol) and miglitol (-5.6 kcal/mol). MD simulations confirmed the stability of the complexes, with RMSD values of 0.21 ± 0.02 nm for 1HE and 0.24 ± 0.03 nm for C4B, showing minimal structural deviations. Structural analyses, including radius of gyration (Rg) and solvent-accessible surface area (SASA), revealed stable and compact protein-ligand conformations. Notably, free energy landscape (FEL) analysis indicated that C4B induces multiple metastable states, suggesting a dynamic inhibitory mechanism potentially involving allosteric regulation. These results highlight 1HE and C4B as promising natural inhibitors with favorable stability, binding characteristics, and inhibitory mechanisms. Further in vitro and in vivo studies are warranted to validate their therapeutic potential as safe and effective alternatives for diabetes management.

Persistent and mobile organic compounds (PMOC) are of great concern for water quality and human health. The recent improvement and availability of high-resolution mass spectrometry in combination with liquid chromatography have widely expanded the potential of analytical workflows for their detection and quantitation in water. Given their high polarity, the detection of some PMOC requires alternative techniques to reversed-phase chromatography, such as hydrophilic interaction liquid chromatography (HILIC) and supercritical fluid chromatography (SFC). Unified chromatography (UC), an SFC gradient in which the state of the mobile phase changes continuously from supercritical to liquid at 100 % polar co-solvent, has shown potential for the analysis of compounds in a broad range of polarity, including very polar compounds.

In the present study, for the first time, a UC-HILIC method coupled with high-resolution mass spectrometry was set up for PMOC analysis in water. SFC and HILIC gradients were run sequentially on the same bare-silica column, with the first separation running to 100 % modifier (UC) followed by a HILIC gradient transitioning to water. The UC and UC-HILIC gradients were previously optimized on a mix of 18 representative PMOC to assess solvent and mobile phase composition and for the instrumental system setup. The final method was employed for the analysis of water samples in comparison with a traditional reversed-phase separation, resulting in a significant increase in the number of annotated polar PMOC, including compounds listed in the Candidate List of substances of very high concern for Authorisation by the European Chemicals Agency.

The proposed approach represents a robust alternative to traditional methods for broadening the chemical space of separation and mass spectrometric detection. The introduction of the HILIC section of the gradient was necessary for the elution of strongly retained compounds on the silica phase, thus also reducing the amount of compounds that would be permanently bound onto the phase of the column, resulting in possible irreproducibility, pressure increase, and loss of efficiency in the compound separation.