جستجوی مقالات مرتبط با کلیدواژه « saccharin » در نشریات گروه « پزشکی »

The role of artificial sweeteners in the occurrence of cancer risk has been widely discussed during the last few decades. Therefore, the aim of the present study was to determine the dynamic and molecular simulation of the interaction of saccharin(SA) with human p53 protein.

The present bioinformatics study was conducted in 2023. The interaction of SA and sodium saccharin (SSA) with the human p53 gene promoter (Pp53g) has already been published in 2019 in two theoretical and experimental sections. But in the present study, the binding ability and the binding site of SA ligand as a synthetic sweetener with human p53 protein (receptor) as a tumor suppressor was theoretically performed. The amino acid residues involved in the interaction, energy free binding and binding constant were determined. Molecular docking was used for molecular interaction calculations. More detailed information about the binding method of the ligand-receptor complex was obtained by molecular dynamics (MD) simulation. The structure and topology file for the human p53 protein extracted from the protein database was created based on the AMBER 99 force field with the GROMACS 5.3.1 program. Acpype/Antechamber program with General AMBER Force Field (GAFF) was used to create structure file and ligand topology in MD simulation. This force field was compatible with the AMBER 99 force field. The simulation time in explicit solvent was 50 ns for SA-p53 protein complex. The collected data were analyzed using different software and compared with the results of related articles.

The results of molecular docking indicated that the SA compound was bound to human p53 protein with a binding energy of -4.55 kcal/mol and a binding constant of 462.18 μM. A hydrogen bond was formed between SA and amino acid Leu137. The conformational changes resulting from MD simulation for the ligand-protein complex showed that SA can bind to Arg196 and His179 as key amino acids of p53 protein in the DNA binding region through two hydrogen bonds. SA can also be placed in the adjacent of amino acids Leu137, Ala138, His179, Asp184 and Met237 through hydrophobic bonds. The values of the plots of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg) for free p53 protein and in the presence of SA ligand show the stable binding of SA to p53 protein.

The present study could provide valuable information about the binding mechanism of SA to human p53 protein as a macromolecule at the molecular level with subatomic details. The results can be useful in determining the potential carcinogenic risk of this sweetener due to its high consumption and the design and synthesis of newer and safer artificial sweeteners.

Background and Zinc (Zn), copper (Cu) and iron (Fe) are essential minerals required for a variety of biomolecules to maintain the normal structure, function, and proliferation of cells. Abnormal metabolism of heavy metals can lead to several chronic pathogenesis. In this study, two new saccharin hydrazide derivatives were synthesized and their chelatory activities were evaluated. Acetic acid ethyl ester and propionic acid ethyl ester derivatives of saccharin were synthesized by the reaction of the starting materials (saccharin) with ethyl bromoacetate and ethyl bromopropionate under the reflux condition and using the dimethylformamide (DMF) as solvent. Ester compounds were stirred with hydrazine hydrate in ethanol and then the products were isolated. The desired hydrazide compounds were purified by thin layer chromatoghraphy. The ultraviolet (UV) spectra of hydrazide products in the absence and presence of ethylenediaminetetraacetic acid (EDTA) were obtained in order to the analysis of chelating activity with Fe2+ and Fe3+, Zn, Cu and alluminium (Al). All products were determined by analytical methods [nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy]. Crystallization method was used for purification of compounds. The reactions’ yields obtained 44 to 46%. Compounds showed good chelatory activites against Fe3+. In presence of EDTA, the reaction of complex production returned back to previous state which suggested less chelating power of the compound. Overall, saccharin derivatives had the ability to chelate Fe3+ more efficient than that of other metals.

This study was done to investigate the relative role of sweetness and comparative effects of different taste sensation of non-caloric sweetener, saccharin, on pain and morphine antinociception by Formalin-test in mice. The Formalin-test was chosen because it measures the response to a long-lasting nociceptive stimulus and thus may closely resemble clinical pain. Twelve day pretreatment of animals with saccharin (0.04%, 0.08%, 0.16%) potentiated the low dose (1.5 mg/kg) of morphine-induced analgesia in early phase significantly but their effects diminished by increasing the concentration of morphine. Also in the early phase of the antinociception recording, all doses of saccharin antagonized the effect of morphine (3 mg/kg) dose-dependently and the effect of high doses of morphine (6-9 mg/kg) was antagonized by dose of saccharin (0.04%) but the effect of morphine (6 mg/kg) potentiated with high concentrations of saccharine (0.08% and 0.16%). All doses of saccharine decreased morphine analgesic effect at a dose of 9 mg/kg. Analgesic effects of low doses of morphine (1.5-3 mg/kg) were decreased by all doses of saccharine in late phase. Different concentrations of saccharin also affected the antagonistic effect of naloxone (0.4 mg/kg) on morphine-induced analgesia in both phases in Formalin-test. The high dose of saccharin (0.16%) potentiated the effect of naloxone in late phase. The obtained results support that hedonic is an important factor in morphine analgesia. Moreover, it seems important to consider sweet taste sensation. It is therefore inappropriate to use different concentrations of sweet saccharin solutions interchangeably.