Peculiarities of 8+2 cycloaddition of acetylenes to indolizines are reviewed. Especially mentioned are indolizines with leaving groups at positions 3 and 5. Cycloaddition to aza- and benzo ...derivatives are reviewed, as well as 1,10-cyclizations and processes leading to cyclazines where indolizines are intermediates. Mechanistic features (adducts and cycloadducts) and theoretical aspects (one- or two-steps mechanism) are reviewed.
Reaction between the derivatives of 6-methyl-beta-nitropyridin-2-one and phenacyl bromides was studied, and the yields observed were extremely low. The pyridones were converted via chloropyridines to ...methoxyderivatives, which were
-phenacylated. N-Phenacyl derivatives of 4,6-dimethyl-5-nitropyridin-2-one under the action of base gave 5-hydroxy-8-nitroindolizine and under acidic conditions gave 5-methyl-6-nitrooxazole3,2-
pyridinium salt, which underwent recycization with MeONa to 5-methoxy-8-nitroindolizine.
Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological ...activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem.
Modern methodology of drugs involves synthesis, physicochemical study, molecular modeling and selection of active compounds through virtual screening and experimental evaluation of the biological activity of new chimeric compounds with pharmacophore fragments. For the synthesis of new compounds, classical organic methods were used and developed. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. For docking analysis, various soft ware packages and methods were used.
As a result of multistep reactions, 11 new, tri- and tetracyclic heterocyclic systems were obtained. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures as well as some psychotropic effects. The biological assays evidenced that nine of the eleven studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of the compounds is low, and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity, it was found that the selected compounds have an activating behavior and anxiolytic effects on the "open field" and "elevated plus maze" (EPM) models. The data obtained indicate the anxiolytic (antianxiety) activity of the derivatives of tricyclic thieno2,3-
pyridines and tetracyclic pyridothieno3,2-
pyrimidin-8-ones, especially pronounced in compounds
-
and
. The studied compounds increase the latent time of first immobilization on the "forced swimming" (FS) model and exhibit antidepressant effects; compounds
and
especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds
and
bound tightly in the active site of γ-aminobutyric acid type A (GABA
) receptors with a value of the scoring function that estimates free energy of binding (∆G) at -10.0 ± 5 kcal/mol. Compound
showed the best affinity ((∆G) at -11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin (SERT) transporter. Compounds
-
and
practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound
((∆G) at -9.3 ± 0.46 kcal/mol).
The selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects.
Currently, special attention is paid to the study of the mechanisms of stress resistance of extremophile organisms that can survive in extreme conditions. Such organisms include lichens, which are ...symbiotic associations of fungi and algae and/or cyanobacteria. The high stress resistance of lichens is due to the presence of a wide range of biologically active metabolites, including sterols. It is known that lichens have a diverse and unique sterol composition, different from that of fungi and algae. Sterol-mediated biochemical mechanisms of stress resistance in lichens have not been fully studied and not systematized. Temperature stress is quite common for lichens, which often grow in unfavorable conditions. It is known that dry lichen thalli are able to withstand temperature changes over large ranges, while hydrated thalli are much more sensitive to unfavorable temperatures. In this work, stress-induced changes in respiratory activity and membrane stability index (MSI), as well as the sterol profile of hydrated lichen thalli, of
Peltigera canina
(L.) Willd. under the influence of elevated (+40°С) and low (–20°С) temperatures was investigated. It was shown that unfavorable temperatures caused a suppression of respiration rate and a decrease in the MSI of lichen thalli. Chromatomass spectrometric analysis showed the presence of
P. canina
ergosterol, dehydroergosterol, episterol, lichesterol, and fungisterol. Under the influence of both stress factors, there was a decrease in the level of ergosterol and an increase in the proportion of episterol. Under cold stress conditions, the proportion of dehydroergosterol also increased, the proportion of lichesterol decreased, and the relative content of the more saturated sterol fungisterol remained at the control level. It can be assumed that stress-induced changes in the sterol profile of lichens under low-temperature exposure create an optimal balance of sterols in membranes, which provides conditions for the deployment of a successful strategy leading to the adaptation of the lichen to the action of a stressor.
The sodium-dependent vitamin C transporter (SVCT2) is responsible for the transport of vitamin C into cells in multiple organs, from either the blood or the cerebrospinal fluid. Mice null for SVCT2 ...(SVCT2
−/−) do not survive past birth but the cause of death has not yet been ascertained. After mating of SVCT2
+/− males and SVCT2
+/− females, fewer SVCT2
−/− and SVCT2
+/− progeny were observed than would be expected according to Mendelian ratios. Vitamin C levels in SVCT2
−/−, SVCT2
+/−, and SVCT2
+/+ were genotype-dependent. SVCT2
−/− fetuses had significantly lower vitamin C levels than littermates in placenta, cortex, and lung, but not in liver (the site of vitamin C synthesis). Low vitamin C levels in placenta and cortex were associated with elevations in several markers of oxidative stress: malondialdehyde, isoketals, F
2-isoprostanes, and F
4-neuroprostanes. Oxidative stress was not elevated in fetal SVCT2
−/− lung tissue despite low vitamin C levels. In addition to the expected severe hemorrhage in cortex, we also found hemorrhage in the brain stem, which was accompanied by cell loss. We found evidence of increased apoptosis in SVCT2
−/− mice and disruption of the basement membrane in fetal brain. Together these data show that SVCT2 is critical for maintaining vitamin C levels in fetal and placental tissues and that the lack of SVCT2, and the resulting low vitamin C levels, results in fetal death and, in SVCT2
−/− mice that survive the gestation period, in oxidative stress and cell death.
In 20222023 in connection with the escalation of the confrontation between the United States and China in Asia-Pacific in both military and political spheres, the position of the countries of East ...and Southeast Asia acquires an extremely important role. A number of regional powers have already taken their side, and the struggle between the two superpowers now aims to attract new allies and partners out of the ASEAN countries. Vietnam as a regional leader and a major economic player in the strategically important Greater Mekong region is of paramount importance to the interests of both the United States and China. Vietnam finds itself in the epicenter of a big diplomatic game between Washington and Beijing. The Chinese leadership can no longer ignore the danger of rapprochement of its Southern neighbors with the military-political associations that the United States forms along the borders of the PRC. The future of not only the two-state dialogue, but also in many respects the security and stability in the Southeast Asia depends on how the Chinese authorities approach the resolution of problems in VietnamChina relations.
The processes of fabrication of nonpolar (11
0) ZnO films with a thickness of up to 7.25 µm on (1
02) sapphire (Al
2
O
3
) substrates with a terrace-step surface nanostructure by magnetron sputtering ...at a growth rate of up to 4.5 nm/s has been studied. The effect of steps in the initial growth stages has been found, which leads to the formation of isolated ZnO nanostructures decorating the steps. In all next growth stages, a continuous (11
0) epitaxial ZnO film with the longitudinal 0001 axis of crystallites, oriented parallel to the step edge on the sapphire surface has been observed. It is established that the interplanar spacing in the ZnO films in the 11
0 direction, determined from the X-ray diffraction data, depends on the thickness and deposition rate and approaches the value of X-ray diffraction references for ZnO with an increase in thickness to 7.25 µm and a decrease in the growth rate to 2.1–2.3 nm/s.
An analysis of the present-day situation in international relations as a conflict of civilizations, namely the two new poles of world politics which are proposed to be identified as the global West ...and the global East, is provided. The historical roots and reasons for this cultural conflict between the two poles are summarized briefly and the role of Russia and China in shaping the new system of international relations, which tends toward a return to bipolarity, is estimated.
The electrochemical properties of nickel(II) ions in the presence of few-layer black phosphorus (FLBP) have been investigated by the method of cyclic voltammetry. It was shown that FLBP is able to ...stabilize electrochemically generated nickel(0) species in solution.
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