Existence of advanced glycation / lipoxidation end-products in parenteral nutrition solutions and effects of infusion conditions on their levels

Abstract Infusion solutions must be stable from the production stage until the infusion stage. Some infusion fluids contain degradation products, known as advanced glycation end products (AGEs); however, it is unknown whether AGEs exist in parenteral nutrition solutions. We aimed to investigate this question and test the effect of infusion conditions on AGE formation in parenteral nutrition solution. Nine parenteral nutrition solutions were supplied by the pharmacy with which we collaborated. To simulate the infusion conditions, the solutions were held in a patient room with standard lighting and temperature for 24 hours. Samples were taken at the beginning (group A) and the end (24th hour, group B) of the infusion period. The degradation products were 3-deoxyglucosone, pentosidine, N-carboxymethyl lysine, and 4-hydroxynonenal, which we investigated by high-performance liquid chromatography-mass spectrometry (LC-MS) and Q-TOF LC/MS methods. Two of four degradation products, 4-hydroxynonenal and N-carboxymethyl lysine, were detected in all samples, and Group B had higher levels of both compounds compared to Group A, who showed that the quantities of these compounds increased in room conditions over time. The increase was significant for 4-hydroxynonenal (p=0.03), but not for N-carboxymethyl lysine (p=0.23). Moreover, we detected in the parenteral nutrition solutions a compound that could have been 4-hydroxy-2-butynal or furanone

An integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking study.

BACKGROUND: This study aims to synthesise and characterise novel compounds containing 2-amino-1,3,4-thiadiazole and their acyl derivatives and to investigate antifungal activities. Similarity search, molecular dynamics and molecular docking were also studied to find out a potential target and enlighten the inhibition mechanism. RESULTS: As a first step, 2-amino-1,3,4-thiadiazole derivatives (compounds 3 and 4) were synthesised with high yields (81 and 84%). The target compounds (6a-n and 7a-n) were then synthesised with moderate to high yields (56-87%) by reacting 3 and 4 with various acyl chloride derivatives (5a-n). The synthesized compounds were characterized using the IR, 1H-NMR, 13C-NMR, Mass, X-ray (compound 7n) and elemental analysis techniques. Later, the in vitro antifungal activities of the synthesised compounds were determined. The inhibition zones exhibited by the compounds against the tested fungi, their minimum fungicidal activities, minimum inhibitory concentration and the lethal dose values (LD50) were determined. The compounds exhibited moderate to high levels of activity against all tested pathogens. Finally, in silico modelling was used to enlighten inhibition mechanism using ligand and structure-based methods. As an initial step, similarity search was carried out and the resulting proteins that belong to Homo sapiens were used as reference in sequence similarity search to find the corresponding amino acid sequences in target organisms. Homology modelling was used to construct the protein structure. The stabilised protein structure obtained from molecular dynamics simulation was used in molecular docking. CONCLUSION: The overall results presented here might be a good starting point for the identification of novel and more active compounds as antifungal agents.

Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents.

In this study, a novel series of phenyl substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans. Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 µg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 µg/ml and 0.85 µg/ml, respectively). Furthermore, structure-activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra-precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron-donating substituents at the second aryl ring is detrimental to activity.

Redox-Switchable New Phthalocyanines Containing Hydrazono-Thiazole-Carboxylate Fragments: Synthesis, Electrochemical, Spectroelectrochemical and Electrocolorimetric Investigation.

New phthalonitrile compound with Schiff base, carbothioamide and thiazole moieties as substituents and its corresponding metal-free and metallophthalocyanines (Zn(II), Ni(II), Co(II), and Cu(II)) were synthesized and characterized for the first time. The solubilities of these novel phthalocyanines were high in organic solvents. The redox properties of the compounds have been researched by cyclic voltammetry, square wave voltammetry, controlled-potential coulometry and in situ spectroelectrochemistry in dimethylsulfoxide. The compounds displayed metal and/or phthalocyanine ring-based, generally reversible or quasi-reversible reduction and oxidation processes. The effect of aggregation on the redox behavior of these complexes was also discussed. In general, decreased intensity and broadening in the main Q absorption band and the appearance of a new blue-shifted band confirmed the presence of H-type aggregates in the solutions of the complexes 4, 6 and 8 in DMSO/TBAP. The color changes associated with the redox processes and electrogenerated anionic and cationic redox species were also recorded with in situ electrocolorimetric measurements. In situ UV-vis spectral and associated color changes monitored during the reduction processes of the complexes suggested their applicability in the fields of the electrochemical technologies.

Novel olefinic-centered macroacyclic compounds involving tetrasubstituted 4-hydroxybenzoic acid fragments: synthesis, structural characterization and comparison of experimental and computational results.

Dialkyl 4,4'-(2-(1,3-bis(4-(alkoxycarbonyl)phenoxy)propan-2-ylidene)propane-1,3-diyl)bis (oxy)dibenzoate 6a,b were synthesized through the reaction of ethene-1,1,2,2,-tetra-yl-tetra methylene tetra bromide 1 with methyl 4-hydroxy benzoate or ethyl 4-hydroxy benzoate 2a,b. In addition, compounds 6a,b were obtained by using the esterification reaction from the reaction compound 5 with methyl and ethyl alcohol in high yields. Compound 4 was synthesized from the reaction of ethene-1,1,2,2,-tetra-yl-tetra methylene tetra bromide 1 with 4-hydroxy benzonitrile 3. The structures of the novel synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, COSY, elemental analysis, and mass spectral data. Compound 6b, C42H44O12, was also characterized with additional analysis such as UV-vis, and X-ray spectral techniques. The electronic structure of compound 6b was studied by DFT level 6-31G∗(d,p) using X-ray crystallographic data. The results obtained from this study are consistent with the X-ray data. In order to understand the electronic transitions of the compound 6b, time dependent density functional theory (TD-DFT) calculations were carried out. TD-DFT studies showed that the low-energy excitations are consistent with the experimental results.

Thermal degradation behavior of methyl methacrylate derived copolymer.

A novel copolymer of 2-hydroxy-3-menthyloxy-1-(4-methoxyphenyl)-3-oxopropyl methacrylate (HMOPMA) and methyl methacrylate (MMA), [poly(HMOPMA-co-MMA)], was synthesized by free radical polymerization. The percentages of HMOPMA and MMA units obtained in the copolymer composition were 19% and 81%, respectively. The solubility parameter of poly(HMOPMA-co-MMA) was found to be 10.3 cal(1/2) cm(-3/2) by turbidimetric titration method. Thermal degradation mechanism and activation energies for initial decomposition process under non-isothermal conditions were determined by integral approximation methods from the thermogravimetric study. The decomposition activation energies of poly(HMOPMA-co-MMA) using Kissinger and Flyn-Wall-Ozawa methods were calculated as 119.99 kJ/mol and 125.34 kJ/mol, respectively. The study of kinetic equations showed that the reaction mechanism of decomposition process in the conversion range studied progressed with D1 mechanism, one-dimensional diffusion of deceleration type of solid state mechanism.

Synthesis, characterization and properties of tetra((1-hydroxyimino-methylnaphthalen-2-yloxy)methyl)ethene and its homo-dinuclear metal complexes: a combined experimental and theoretical investigation.

Tetra((1-hydroxyiminomethylnaphthalen-2-yloxy)methyl)ethene (THIMNYOME), H(4)L, was synthesized by the agents of 2-hydroxy-1-naphtaldehyde, tetra(bromomethyl)ethene and hydroxylamine hydrochloride in two steps. Characterization of THIMNYOME and its dinuclear complexes was made by elemental analyses, IR, (1)H- and (13)C NMR, UV-vis, electrospray ionisation mass spectra, molar conductivities and magnetic susceptibility measurements. In the light of these results, it was suggested that the ligand coordinate to each metal atom by the two ether oxygen, two nitrogen atoms of oxime imine (CN) and an axial oxygen of perchlorate to form pseudo square-pyramidal complexes with Ni(II), Cu(II) and Zn(II). Molar conductivity measurements reveal that all the complexes are non-electrolytes. In addition, the full geometric optimization of the tetraoxime ligand (4) has been made by the B3LYP/6-31G(d) level in order to establish a stable conformation. Additionally, all the complex structures have been studied in the B3LYP/LANL2DZ level. NBO charge distribution and the characteristics of frontier molecular orbitals of these complexes have also been investigated in order to see the electrons movement between ligand and metal atom in the same level.

Synthesis and characterization of some new tetraaldehyde and tetraketone derivatives and X-ray structure of 1,1'-(4,4'-(2-(1,3-bis(4-acetylphenoxy)propan-2-ylidene)propane-1,3-di-yl)bis(oxy)bis(4,1-phenylene))diethanone.

Tetraketone and tetraaldehyde derivatives 2a-d were synthesized via the reaction of ethene-1,1,2,2,-tetra-yl-tetramethylene tetrabromide (1) with hydroxyketone and aldehyde derivatives. The molecular structures were identified by IR, (1)H-NMR, (13)C-NMR and MS analysis. The crystal structure of the title compound 2a, C(38)H(36)O(8), is reported. Its crystal data are: monoclinic, space group P 2(1)/n with cell dimensions of a=9.0395(12) A, b=12.6114(17) A, c=13.8166(18) A, beta=95.875(3), V=1566.8(4) A(3), F.W.=620.67, rho(calc)=1.316 gcm(3) for Z=2, mu=0.092 mm(-1).

4,4'-Butane-1,4-diylbis[3-ethyl-1H-1,2,4-triazol-5(4H)-one] and 4-hydroxy-3-n-propyl-1H-1,2,4-triazol-5(4H)-one.

The title compounds, C12H20N6O2, (I), and C5H9N3O2, (II), display the characteristic features of 1,2,4-triazole derivatives. Compound (I) lies about an inversion centre which is at the mid-point of the central C-C bond. Compound (II) also contains a planar 1,2,4-triazole ring but differs from (I) in that it has a hydroxy group attached to the ring. Molecules of (I) are held together in the crystal structure by intermolecular N-H...O contacts and by weak pi-pi stacking interactions between the 1,2,4-triazole moieties. Compound (II) contains intermolecular O-H...O and N-H...O hydrogen bonds.

Nitric oxide levels in tears of patients with mild forms of papillary conjunctivitis induced by rigid gas-permeable contact lenses.

PURPOSE: To determine whether nitric oxide (NO) is detectable in the tear fluid of patients with mild forms of papillary conjunctivitis who wear rigid gas-permeable contact lenses. METHODS: Tear samples were taken from 12 users of rigid gas-permeable contact lenses and 12 healthy controls. Samples were analyzed, and the levels of NO were determined. RESULTS: The mean level of NO in those who wore contact lenses was 118.98 micromol/L (95% CI: 91.85-146.10 micromol/L); whereas the level of NO found in the control subjects was 114.84 micromol/L (95% CI: 102.54-127.14 micromol/L). The difference was statistically insignificant (P>0.05). CONCLUSION: Nitric oxide levels in the tear fluid of rigid gas-permeable contact lens users did not correlate with the presence of mild symptoms of papillary conjunctivitis.