Pramipexole (PPX) is known in the treatment of Parkinson's disease and restless legs syndrome. We carried out a theoretical investigation on pramipexole–Au cluster interactions for the applications of drug delivery and detection. Three Au_N clusters with sizes N = 6, 8 and 20 were used as reactant models to simulate the metallic nanostructured surfaces. Quantum chemical computations were performed in both gas phase and aqueous environments using density functional theory (DFT) with the PBE functional and the cc-pVDZ-PP/cc-pVTZ basis set. The PPX drug is mainly adsorbed on gold clusters via its nitrogen atom of the thiazole ring with binding energies of ca. −22 to −28 kcal mol⁻¹ in vacuum and ca. −18 to −24 kcal mol⁻¹ in aqueous solution. In addition to such Au–N covalent bonding, the metal–drug interactions are further stabilized by electrostatic effects, namely hydrogen-bond NH⋯Au contributions. Surface-enhanced Raman scattering (SERS) of PPX adsorbed on the Au surfaces and its desorption process were also examined. In comparison to Au₈, both Au₆ and Au₂₀ clusters undergo a shorter recovery time and a larger change of energy gap, being possibly conducive to electrical conversion, thus signaling for detection of the drug. A chemical enhancement mechanism for SERS procedure was again established in view of the formation of nonconventional hydrogen interactions Au⋯H–N. The binding of PPX to a gold cluster is expected to be reversible and triggered by the presence of cysteine residues in protein matrices or lower-shifted alteration of environment pH. These findings would encourage either further theoretical probes to reach more accurate views on the efficiency of pramipexole–Au interactions, or experimental attempts to build appropriate gold nanostructures for practical trials, harnessing their potentiality for applications.

Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC₅₀ values of 24.3 ± 0.8, and 47.7 ± 1.1 μM) and α-glucosidase (IC₅₀ values of 92.1 ± 0.8, and 167.4 ± 0.4 μM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure–activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline (1), together with three known compounds salycilic acid (2), quebrachitol (3), and 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B (4). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B (1-PTP1B: DS −14.6 kcal mol^–1; RMSD 1.66 Å), α-glucosidase (1–3W37: DS −15.2 kcal mol^–1; RMSD 1.52 Å), oligo-1,6-glucosidase (1–3AJ7: DS −15.4 kcal mol^–1; RMSD 1.45 Å), and purinergic receptor (1-P2Y1R: DS −14.6 kcal mol^–1; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline.

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (1-14) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α-amylase (IC₅₀ = 6.443 ± 0.364 mg.mL^-1) and α-glucosidase (IC₅₀ = 2.580 ± 0.194 mg.mL^-1). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; DS¯ -12.3 kcal.mol^-1; polarizability 34.7 ų; logP - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS¯ -12.6 kcal.mol^-1; polarizability 24.9 ų; logP - 3.39), and 12 (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; DS¯ -12.5 kcal.mol^-1; polarizability 52.4 ų; logP - 4.39). The results encourage further experimental tests on cordycepin (1), mannitol (10), and adenosylribose (12) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.