Biological behavior of a new 68Ga-labelled glucose derivative as a potential agent for tumor imaging

Glucose analogs and derivatives labeled with positron emitter 68Ga are considered to be a promising alternative to widely used radiotracer 18F-FDG for tumor PET imaging. In this study a biodistribution of a new glucose derivative labeled with 68Ga (68Ga-NODA-thioglucose) was investigated. All biodistribution studies were carried out in Balb/c mice with experimental model of tumor or aseptic inflammation. The tumor uptake of 68Ga-NODA-TG decreased throughout the study from 3.00±0.08 % ID/g to 1.06±0.04 %ID/g. The peak amount of 68Ga-NODA-TG in muscle with inflammation reached 4.33±0.12 % ID/g, decreasing to 0.23±0.08 % ID/g. In other organs and tissues the biodistribution of 68Ga-NODA-TG was similar in tumor-bearing mice and mice with aseptic inflammation. In conclusion, the obtained results suggest that 68Ga-NODA-TG has the potential for clinical application as a PET tracer.

An Efficient Synthesis of Tetrodotoxin

Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.

A Novel Fluorescence “Turn-Off” Sensor Base On A Triazole-Linked BINOL-Glucose Derivative For The Sensitive Detection of Copper Ion

A novel sensitive chiral fluorescent “turn-off” sensor based on 3,3′-positions modified triazole-linked BINOL-Glucose derivative has been synthesized via “click” reaction. The fluorescence emission intensity of (S, β-D)-1 was almost completely quenched along with obvious color change from yellow to green upon the coordination with a Cu(II) ion while other metal ions had no obvious change. The detection limit of the sensor (S, β-D)-1 toward copper ion was calculated to be 0.31 μmol L-1. The stoichiometry ratio of (S, β-D)-1-Cu2+ complex was proved to be 1:1 by the analysis of NMR spectroscopic, ESI-MS data and the job’s plot. HNMR spectroscopic and IR were also used to study the mechanism, demonstrated copper ion was coordinated with (S, β-D)-1 by 1+1complex formation.

Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates

Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form.

Synthesis and evaluation of modified siRNA molecules containing a novel glucose derivative

Chemical modifications are critical for the development of safe and effective siRNAs for downstream applications.

Study of Pharmacokinetics of a New Radiopharmaceutical on the Basis of Technetium-99m Labeled Glucose

Purpose: To study the features of the distribution and removal of a new radiopharmaceutical (RPH) on the basis of a labeled 99mTc glucose derivative for radionuclide diagnostics of oncological diseases in the body of experimental animals. Material and methods: The main stage of the study was performed on 65 mature conventional outbred white rats and 9 rabbits of the Soviet Chinchilla breed. To study the dynamics of changes in the concentration of the studied RPH in the blood plasma and its distribution in the main organs and tissues, as well as to study the metabolic features of the drug and its excretion, the RPH studied was administered intravenously, once in activity of 20 MBq. Multiple introduction of the RPH was performed in order to study the cumulative properties of the study drug, and to elucidate the possibilities of predicting the cumulation processes from the data obtained with a single administration of RPH. For this purpose, intravenous RPH was administered at the same time 1 time / day for 5 days, at a dose of 20 MBq. To confirm the theory of linearity of the pharmacokinetics of the RFP studied, three groups of laboratory animals received the drug in three activity levels – 10, 20 and 40 MBq were used. After euthanasia, the animals were autopsied and removed the necessary organs and tissues. The prepared and washed organs were placed in tubes for further radiometry in order to study the concentrations of the RPH in the bioassay. Results: It has been established that the RPH being studied practically does not accumulate in the main organs and tissues, accumulating mainly in the kidneys and bladder. The main organs of elimination of the test drug are the kidneys, and the main excreta are urine. The half-life of the drug from the blood was 10 minutes. Pharmacokinetics of the drug is linear and does not depend on the administered activity, and the drug itself does not possess cumulative properties. Conclusion: A study of the pharmacokinetics of the RPH 99mTc-1-Thio-D-glucose showed that the preparation possesses optimal properties for the diagnostic agent. The drug stably does not accumulate in the main organs and tissues, which allows it to be reused, for example at the stages of dynamic observation of cancer patients.