Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations.

In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the benzene ring.

Spiro[3.3]heptane as a Saturated Benzene Bioisostere.

The spiro[3.3]heptane core, with the non-coplanar exit vectors, was shown to be a saturated benzene bioisostere. This scaffold was incorporated into the anticancer drug sonidegib (instead of the meta-benzene), the anticancer drug vorinostat (instead of the phenyl ring), and the anesthetic drug benzocaine (instead of the para-benzene).

In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology.

Photocontrolled, biologically active compounds are an emerging class of "smart" drug candidates. They provide additional safety in systemic chemotherapy due to their precise spatiotemporal activation by directing a benign, non-ionizable light to a specific location within the patient's body. This paper presents a set of methods to evaluate the in vitro potency and ex vivo efficiency of the photoactivation of photocontrolled, biologically active compounds as well as the in vivo efficacy at early stages of drug development.

1-Azaspiro[3.3]heptane as a Bioisostere of Piperidine.

1-Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO S-NCO, to give spirocyclic β-lactams.

Oxa-spirocycles: synthesis, properties and applications.

A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared.

Phosphine Oxides (-POMe) for Medicinal Chemistry: Synthesis, Properties, and Applications.

A general practical approach to hetero(aromatic) and aliphatic P(O)Me-substituted derivatives is elaborated. The key synthetic step was a [Pd]-mediated C-P coupling of (hetero)aryl bromides/iodides with HP(O)Me. The P(O)Me substituent was shown to dramatically increase solubility and decrease lipophilicity of organic compounds.

Effect of Long-Term Treatment with C Fullerenes on the Lifespan and Health Status of CBA/Ca Mice.

Several studies claimed C fullerenes as a prospective geroprotector drug due to their ability to capture free radicals effectively and caused a profound interest in C in life extension communities. Multiple additives are already sold for human consumption despite a small body of evidence supporting the beneficial effects of fullerenes on the lifespan. To test the effect of C fullerenes on lifespan and healthspan, we administered C fullerenes dissolved in virgin olive oil orally to 10-12 months old CBA/Ca mice of both genders for 7 months and assessed their survival.

Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery.

The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps-synthesis of azetidinones, and reduction into azetidines.

1-Substituted 2-Azaspiro[3.3]heptanes: Overlooked Motifs for Drug Discovery.

The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs), however, their spirocyclic analogues remain unknown. Described here is the synthesis of spirocyclic analogues for 2-substituted piperidines and a demonstration of their validation in drug discovery.

Induction of neonatal tolerance to GFP-labeled karyocytes in C57/B6 mice.

Green fluorescent protein is widely used in biological studies including parabiosis models for visualization of cellular structures and cells. However, the growing number of the data is available regarding immunogenicity of this protein, which can interfere with its use in in vivo experiments. In this study, we attempted to induce neonatal immunological tolerance to GFP-labeled karyocytes by intraperitoneal injections of B6.

Aged mice repeatedly injected with plasma from young mice: a survival study.

It was reported using various biological models that the administration of blood factors from young animals to old animals could rejuvenate certain functions. To assess the anti-aging effect of young blood we tested the influence of repeated injections of plasma from young mice on the lifespan of aged mice. One group of 36 CBA/Ca female mice aged 10-12 months was treated by repeated injections of plasma from 2- to 4-month-old females (averaging 75-150 μL per injection, once intravenously and once intraperitoneally per week for 16 months).

[ApoE gene polymorphism as a predictor of therapeutic response to treatment acetylcholinesterase inhibitor for elderly patients with Alzheimer's and vascular dementia types].

Unlabelled: Effectiveness of donepezil hydrochloride treatment for elderly patients with Alzheimer's and vascular dementia types depending on the ApoE genotype.

The Aim: To study the effectiveness of donepezil hydrochloride (Almer "Actavis") for elderly patients with Alzheimer's and vascular dementia types depending on the ApoE genotype.

Methods And Subjects: The 3-month clinical study included 38 elderly patients (mean age- (71.

Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis.

The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.

[The activity of gas metabolism, thermoregulation, and antioxidant enzymes in aging C57Bl/6 mice].

The distribution type and correlative links between physiological and biochemical indices characterizing functional condition of the systems of gaseous exchange (V(O2) and V(CO2)), thermoregulation (body temperature and coefficient of thermoconductivity) and antioxidant defense have been studied in 62 young (3-5 mo.) and 58 old (23-26 mo.) male C57Bl/ 6 mice.

[Increase in T-cell level in the peripheral blood of women with fractures in anamnesis during postmenopause period].

44 postmenopausal patients (45-76 years of old) have been observed. Interrelationship between composition and functional activity of peripheral blood cells, TNF-alpha level in the serum and bone density in postmenopausal women has been analyzed. It was established that the increase in neutrophil activity in women with osteoporosis, the high level of immune complexes are accompanied by the high level of IgG and autoantibodies to DNA.

[Role of genetic factors in the development of osteoporosis].

Osteoporosis which often accompanies the normal aging and a number of pathological conditions is closely related to bone remodeling disturbances. This process is provided mainly by the genesis of osteoblasts and osteoclasts, their activities and interactions. All the above in turn is dependent on numerous systemic and local regulatory factors such as hormones, nutrients, minerals, vitamins, cytokines, their receptors etc.

[Catalase and glutathione-peroxidase: qualitatively different correlations with the rate of oxygen consumption].

Correlative relations of the liver supernatant enzymatic activity of catalase (CAT) and glutathione-peroxidase (GP) with the velocities of oxygen consumption (VO2) and carbon dioxide exhalation (VCO2) were analyzed by the two- and three-dimensional linear and non-linear statistical methods in mice. It is shown that despite the close functions, CAT and GP, nevertheless, exhibit opposite correlative and regressive links with the gaseous exchange indices. As was found by the pairwise linear method, the activity correlation with VO2 was positive for CAT, but negative for GP.

Superoxide dismutase, catalase and glutathione peroxidase activities in the liver of young and old mice: linear regression and correlation.

Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) were determined in the liver of 15 young (3-5 months) and 15 old (23-26 months) female CBA mice. Although, the activities of all three enzymes decreased in aging, only the SOD decline was statistically significant (P<0.01).

[Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors].

Studies were undertaken on the development of T-lymphocytes in adult and old CBA mice and its changes at aging after injections of pineal gland peptides. It was shown that in old mice the disturbances of T-cells differentiation are registered in bone marrow, thymus, spleen and characterized by the changes of lymphocyte markers expression, migration and proliferation of cells. In old mice FTS titer, melatonin and testosterone levels decreased, the balance of noradrenalin and serotonin in hypothalamus and the cell composition of microenvironment immune systems organs impaired.

[Correlative links between superoxide dismutase, catalase and glutathione peroxidase activities in mouse liver].

Qualitative and quantitative differences in correlative and regressive links between superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase were assessed in the mice liver by two- and three-dimensional statistical methods. Paired linear correlation analysis indicated SOD-CAT tandem as the correlatively acting enzymatic pair. Three-dimensional analysis revealed uniform response surfaces which exhibited higher activities at disproportional values of the other two and lower activities at proportional activities of the other two enzymes.

Pair-wise linear and 3D nonlinear relationships between the liver antioxidant enzyme activities and the rate of body oxygen consumption in mice.

Relationships between the rate of body oxygen consumption (VO2) and the liver key antioxidant enzyme activities were assessed in female CBA mice. The pair-wise linear regression and correlation demonstrated significant correlative links between VO2 and activity of catalase (CAT). Nonlinear 3D plotting revealed a complementary pattern of CAT and glutathione peroxidase (GP) relation.