Neurotropic Activity Research Articles

Neuroprotective Activity of GLP-1 Analogues: General Understanding of Implementation Mechanisms

Glucagon-like peptide-1 (GLP-1) is a hormone possessing extensive pharmacologic potential. Additionally, to its multiple metabolic effects, GLP-1 also exhibits cardiac and neuroprotective effects. Native GLP-1 is not used as a medicinal agent, however, now GLP-1 analogues structurally similar to it and having a long-lasting effect have been developed and used in the treatment of type 2 diabetes mellitus (T2DM). The review focuses on the neuroprotective effect of these drugs and discusses possible mechanisms of this effect. Aim: To identify information about experimental and clinical evidence about the role of GLP-1 analogues in brain protection in neurodegenerative dis[1]eases. Materials and Methods: The review was performed in accordance with the PRISMA 2020 statement; publications were searched for in the PubMed, MedLine, Web of Science, Scopus, and Google Scholar databases covering the period from 2014 to 2024. Results: The publications provide strong evidence of the association between T2DM and cognitive impairment, as well as information on the effectiveness of GLP-1 analogues in the management of neurodegenerative diseases. Possible mechanisms are discussed. Conclusion: This review shows that GLP-1 can prevent cognitive and motor disorders. There is sufficient experimental evidence of the neurotropic activity of the drugs, and clinical trials are ongoing.

Synthesis and Evaluation of the Neurotropic Activity of New β-Cycloketol Derivatives

Synthesis and Evaluation of the Neurotropic Activity of New β-Cycloketol Derivatives

Влияние фосфорсодержащих пестицидов на ферментативную активность и множественные формы кислой фосфатазы живородки речной (Viviparus viviparus L.)

Organophosphate pesticides are used in agriculture and for treating landscape and park areas due to their high efficiency and economic availability, and therefore they are potential toxicants in water bodies. Broad-spectrum systemic herbicide (Glyphosate) and an organophosphorus insecticide (Malathion) have been studied against the freshwater mollusks (Viviparus viviparus L.), widespread in permanent water bodies of the European part of Russia and Siberia. Changes in the activity and composition of multiple forms of acid phosphatase (AcP) were revealed in the hepatopan creas of mollusks under the influence of high doses of glyphosate and malathion in an acute toxicological experiment (96 hours). In both cases, an increase in enzyme activity is observed, but the cholinomimetic malathion is significantly more active than glyphosate, the neurotropic activity of which is unknown. It was shown that the increase in activity in the experimental groups of mollusks is associated with the appearance of new multiple forms of acid phosphatase, which persist throughout the experiment. Multiple form of AсP with low relative electrophoretic mobility revealed as an effect of glyphosate and malathion. In addition, in mollusks exposed to malathion, a multiple form of the enzyme with an average electrophoretic mobility was detected. The composition of multiple forms of acid phosphatase in mollusks of the control group did not change during the exposure. The results indicate the formation of nonspecific adaptations in response to organophosphate pesticides and confirm that acid phosphatase can be an indicator of toxic effects in environmental and biochemical monitoring of freshwater pollution.

Synthesis and Psychotropic Properties of Novel Condensed Triazines for Drug Discovery.

The exploration of heterocyclic compounds and their fused analogs, featuring key pharmacophore fragments like pyridine, thiophene, pyrimidine, and triazine rings, is pivotal in medicinal chemistry. These compounds possess a wide array of biological activities, making them an intriguing area of study. The quest for new neurotropic drugs among derivatives of these heterocycles with pharmacophore groups remains a significant research challenge. The aim of this research work was to develop a synthesis method for new heterocyclic compounds, evaluate their neurotropic and neuroprotective activities, study histological changes, and perform docking analysis. Classical organic synthesis methods were used in the creation of novel heterocyclic systems containing pharmacophore rings. To evaluate the neurotropic activity of these synthesized compounds, a range of biological assays were employed. Docking analysis was conducted using various software packages and methodologies. The neuroprotective activity of compound 13 was tested in seizures with and without pentylenetetrazole (PTZ) administration. Histopathological examinations were performed in different experimental groups in the hippocampus and the entorhinal cortex. As a result of chemical reactions, 16 new, tetra- and pentacyclic heterocyclic compounds were obtained. The biologically studied compounds exhibited protection against PTZ seizures as well as some psychotropic effects. The biological assays evidenced that 13 of the 16 studied compounds showed a high anticonvulsant activity by antagonism with PTZ. The toxicity of the compounds was low. According to the results of the study of psychotropic activity, it was found that the selected compounds have a sedative effect, except compound 13, which exhibited activating behavior and antianxiety effects (especially compound 13). The studied compounds exhibited antidepressant effects, especially compound 13, which is similar to diazepam. Histopathological examination showed that compound 13 produced moderate changes in the brain and exhibited neuroprotective effects in the entorhinal cortex against PTZ-induced damage, reducing gliosis and neuronal loss. Docking studies revealed that out of 16 compounds, 3 compounds bound to the γ-aminobutyric acid type A (GABAA) receptor. Thus, the selected compounds demonstrated anticonvulsant, sedative, and activating behavior, and at the same time exhibited antianxiety and antidepressant effects. Compound 13 bound to the GABAA receptor and exhibited antianxiety, antidepressant, and neuroprotective effects in the entorhinal cortex against PTZ-induced changes.

Thiazolium salt mimics the non-coenzyme effects of vitamin B1 in rat synaptosomes

Long-term studies have confirmed a causal relationship between the development of neurodegenerative processes and vitamin B1 (thiamine) deficiency. However, the biochemical mechanisms underlying the high neurotropic activity of thiamine are not fully understood. At the same time, there is increasing evidence that vitamin B1, in addition to its coenzyme functions, may have non-coenzyme activities that are particularly important for neurons. To elucidate which effects of vitamin B1 in neurons are due to its coenzyme function and which are due to its non-coenzyme activity, we conducted a comparative study of the effects of thiamine and its derivative, 3-decyloxycarbonylmethyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride (DMHT), on selected processes in synaptosomes. The ability of DMHT to effectively compete with thiamine for binding to thiamine-binding sites on the plasma membrane of synaptosomes and to participate as a substrate in the thiamine pyrophosphokinase reaction was demonstrated. In experiments with rat brain synaptosomes, unidirectional effects of DMHT and thiamine on the activity of the pyruvate dehydrogenase complex (PDC) and on the incorporation of radiolabeled [2–14C]pyruvate into acetylcholine were demonstrated. The observed effects of thiamine and DMHT on the modulation of acetylcholine synthesis can be explained by suggesting that both compounds, which interact in cells with enzymes of thiamine metabolism, are phosphorylated and exert an inhibitory/activating effect (concentration-dependent) on PDC activity by affecting the regulatory enzymes of the complex. Such effects were not observed in the presence of structural analogues of thiamine and DMHT without a 2-hydroxyethyl substituent at position 5 of the thiazolium cycle. The effect of DMHT on the plasma membrane Ca-ATPase was similar to that of thiamine. At the same time, DMHT showed high cytostatic activity against neuroblastoma cells.

Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

Synthesis, evaluation of biological activity and SAR of new thioalkyl derivatives of pyridine

BackgroundPyridine and its derivatives play a vital role in medicinal chemistry, serving as key scaffolds for drugs. The ability to bind to biological targets makes pyridine compounds significant, sparking interest in creating new pyridine-based drugs. Thus, the purpose of the research is to synthesize new thioalkyl derivatives of pyridine, predict their biological spectrum, study their psychotropic properties, and based on these findings, perform structure–activity relationships to assess pharmacophore functional groups. MethodsClassical organic methods were employed for synthesizing new thioalkyl derivatives of pyridine, with a multifaceted pharmacological profiles. Various software packages and methods were employed to evaluate the biological spectrum of the newly synthesized compounds. 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. ResultsEffective synthetic methods for 6-amino-4-phenyl-2-thio-2H-thiopyran-5-carboxylic acid ethyl ester, 2-amino substituted thiopyridine derivatives and 6-cycloamino-2-thioalkyl-4-phenylnicotinate derivatives were obtained in high yield. Predicted biological spectra and pharmacokinetic data indicated high gastrointestinal absorption and low blood–brain barrier passage for most compounds and demonstrated potential various biological effects, particularly psychotropic properties. Studied compounds demonstrated high anticonvulsant activity through antagonism with pentylenetetrazole. They exhibited low toxicity without inducing muscle relaxation in the studied doses. In psychotropic studies, the compounds displayed activating, sedative, and anxiolytic effects. Notably, the 6-amino-2-thioalkyl-4-phenylnicotinate derivatives demonstrated significant anxiolytic activity (about four times more compared to diazepam). They also exhibited pronounced sedative effects. Ethyl 2-({2-[(diphenylmethyl)amino]-2-oxoethyl}thio)-4-phenyl-6-pyrrolidin-1-ylnicotinate exhibited anxiolytic activity even two times greater than diazepam. Moreover, all studied compounds showed statistically significant antidepressant effects. Noteworthy ethyl 2-({2-oxo-2-[(tetrahydrofuran-2-ylmethyl)amino]ethyl}thio)-4-phenyl-6-pyrrolidin-1-ylnicotinate showcasing its unique psychotropic effect. ConclusionsThe selected compounds demonstrate anticonvulsant properties, activating behavior, and anxiolytic effects, while simultaneously exhibiting antidepressant effects and these compounds as promising candidates for further exploration in the development of therapeutics with a broad spectrum of neuropsychiatric applications.

Development of Neuroprotective Agents for the Treatment of Alzheimer's Disease using Conjugates of Serotonin with Sesquiterpene Lactones.

Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties. The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones. Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities. The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H2O2. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory. In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.

Synthesis and anticonvulsive activity of new 1,3-diazaadamantane derivatives

The work is devoted to the synthesis and study of the neurotropic activity of some derivatives of 3,7-diazabicyclo/3.3.1/nonanes. For this, various 5,7-dialkyl, methylphenyl, diphenyl 1,3-diazaa-damantanes 1 were synthesized, which, upon interaction with acid chlorides of aliphatic, aromatic and heterocyclic acids, were converted into the corresponding 3,7-diazabicyclo/3.3.1/nonanes. The anticonvulsant activity of the synthesized compounds was studied. Among them, substances with pronounced anticorazole activity were identified.

Neurophysiological and Vascular Mechanisms of Action of the Serotoninergic Drugs for Abortive Migraine Treatment

Abstract—Migraine is a form of primary headache that affects at least 10% of the world’s population. In addition to recommendations for modifying the patient’s lifestyle, migraine management involves stopping an attack that’s already occurred and/or preventing its occurrence. In the abortive treatment of this cephalalgia, both non-specific (eg, non-opioid analgesics) and specific pharmacological agents, can be used. The latter include, in particular, serotonergic drugs of the classes of triptans (selective 5-HT1B/1D receptor agonists), ditans (selective 5-HT1F-mimetics), and ergot alkaloids (non-selective modulators of various 5-HT receptor subtypes). The review discusses the currently availably results of numerous basic and applied studies of these drug groups, in which the neuronal and vascular components of their antimigraine pharmacodynamics were identified. A significant part of the information was obtained in vivo on the various experimental models of migraine based on the trigeminovascular theory of its pathogenesis. Other data are the results of ex vivo studies on isolated tissues and cell cultures. When analyzing these experimental results, evidence is provided in favor of similar mechanisms for realizing the antimigraine potential of all representatives belonging to the pharmacological classes listed, the neurotropic activity of which prevails over their direct intervention in vascular tone. At the same time, special attention is paid to the controversial and debatable issues in this area, the successful solution of which is a key to further progress in the pharmacotherapy of migraine.

Semax as a modulator of the psycho-emotional status of rats in an experimental model of depression based on stress

In modern physiology, the priority direction is the study of the influence of various types of stress, leading, as a rule, to the development of depressive states, on the physiological systems of the body. The main methods for assessing the neuroprotective effect, which is the main component of defense against stress, include the study of behavioral reactions that reflect motor, emotional, and cognitive changes. The study of drugs based on regulatory peptides is promising. Semax (ACTH4-7PGP) is a representative of a new synthetic peptide engineering, practically devoid of a hormonal effect and completely preserving the neurotropic activity of adrenocorticotropic hormone. The aim of the work was an experimental study of the effect of semax on the behavior of animals under the influence of experimental depression based on “social” stress. Material and methods. The study was carried out on 50 outbred male rats aged 6 months. Semax effects were studied under conditions of sensory contact - a model of experimental depression based on the formation of aggressive and submissive behavior in animals, using the multicomponent model the Suok test (“ropewalking”) and the Porsolt test to assess the depressive behavior of rats. Results and its discussion. Intermale confrontations led to a decrease in the time spent in the light half of the test, the number of “exploratory” downward glances, directional head movements; a decrease in the number of visited segments in the light section in victims and aggressors. As a whole, the study of behavioral reactions in animals in the Suok test and the Porsolt test in the model of experimental depression (sensory contact) showed the formation of an anxious-depressive state in animals, which was confirmed by a decrease in the motor and exploratory activity of rats. The results were obtained during the Porsolt test, indicating the formation of a depressive state in animals, which was confirmed by an increase in the total period of immobility in both aggressors and victims, an increase in the time of passive swimming, and a decrease in the time of active swimming. With a comprehensive assessment of animal behavior indicators in the Suok test, against the background of a decrease in the level of anxiety under the influence of semax, an improvement in the parameters of exploratory behavior was observed, in the Porsolt test – of motor activity indicators. Conclusions. Investigation of semax effect on the behavioral reactions of animals under conditions of sensory contact indicates that this drug exhibits an anxiolytic and antidepressant effect, eliminating pathological changes in the psycho-emotional status of animals.

Immunomodulatory and neurotropic activities of synthetic peptides in a model of brain injury in rats

Treatment of consequences of traumatic brain injury (TBI) remains one of the current problems of medicine. To increase the effectiveness of treatment of post-traumatic complications, various drugs are recommended, including the peptide with neuromodulatory activity Semax.The present study aims to determine the presence of neuro- and immunoprotective properties of the synthetic peptide PR5, composed of fragments of proline-rich antimicrobial peptides.The work was performed on male Wistar rats weighing 300-350 g. The “falling weight” model of mechanical brain injury was used, which mainly causes diffuse brain damage. The synthesized peptide PR5, composed of fragments of known proline-rich peptides of animal neutrophils, and the peptide preparation Semax in the form of a 1% aqueous solution were used. The drugs were administered intranasally 1 hour after TBI, then twice a day for 4 days at a dose of 100 mg/kg body weight. Control animals received physiological saline in the same regimen as the peptide preparations.TBI led to a significant decrease in body weight, but in rats receiving the peptide preparation Semax, the decrease in body weight was significantly less than in control animals, and the PR5 preparation completely prevented the decrease in body weight after TBI. After TBI, the proliferative activity of lymphocytes was suppressed and the cytotoxicity of NK cells decreased. In animals treated with peptide preparations, there was no significant suppression of NK cell cytotoxicity, and the proliferative activity of lymphocytes was restored to the level of control animals by day 14 after TBI. Both peptide preparations used contributed to higher locomotor activity, and in animals treated with the PR5 peptide, this type of activity reached the parameters of control animals. The reduction in freezing duration in groups treated with peptide preparations indicates the presence of a sedative effect.The peptide preparation PR5 was active in this series of experiments, showing immunotropic and neuroprotective activity comparable to the Semax preparation. Further studies aimed at confirming the identified types of activity of the peptide preparation PR5 may justify its prospects for clinical use as a new nootropic agent.

New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking.

The synthesis of new original bicyclic pyridine-based hybrids linked to the 1,2,3-triazole unit was described via a click reaction. The anticonvulsant activity and some psychotropic properties of the new compounds were evaluated. The biological assays demonstrated that some of the studied compounds showed high anticonvulsant and psychotropic properties. The five most active compounds (7a, d, g, j, and m) contain a pyrano [3,4-c]pyridine cycle with a methyl group in the pyridine ring in their structures. Furthermore, molecular docking studies were performed, and their results are in agreement with experimental data.

Comparative study of pharmacokinetics and enzymatic resistance of the neuroprotective mean GZK-111 and noopept in rats

The article presents the results of studying the pharmacokinetics and enzymatic stability of a new pharmacologically active compound GZK-111– N-phenylacetyl-glycyl-L-proline ethyl ether in comparison with noopept – N-phenylacetyl-L-prolyl-glycine ethyl ether in rats. It has been shown that both compounds are intensively metabolized in the body of experimental animals, while one of the main active metabolites of both compounds is cyclo-L-prolylglycine (CPG), which has similar neurotropic activity, but the intensity and speed of its formation during metabolic transformations is significantly more pronounced in GZK-111 compared to noopept. The significance of CPG in the realization of the main neurotropic effects of the studied compounds in the experiment in rats is shown.

Combined effect of succinic acid, riboxin, nicotinamide, riboflavin for the treatment of chronic brain ischaemia

Introduction. Сhronicbrain ischaemiais associated with the generation of oxygen free radicals resulting in a condition of oxidativestress. Various studies have investigated that antioxidant compounds can neutralize reactive oxygen species and free radicals.Aim. To evaluate effect of Cytoflavin (INN: inosine + nicotinamide + riboflavin + succinic acid) for the treatment of chronic brain ischemia.Materialy and methods. In a double-blind, placebo-controlled clinical study 50 patients aged 61 ± 9 years with chronic brain ischemia (vascular cognitive impairment), were randomized into Cytoflavin (n = 32) group or placebo (n = 18) group. The sealed envelopes system was used to randomize patients; 10.0 ml of the compound were infused by drops intravenously for 10-day period. During the course of treatment, therapy with vasoactive, nootropic and psychotropic drugs was excluded. In addition to clinical evaluation were carried outa comprehensive neuropsychological testing of cognitive functions, registration of cognitive induced potentials (IP) P300 and study of cerebral hemoperfusion using single photon emission computed tomography. To assess the intensity of lipid peroxidation we estimated several kinetic parameters of ferrous iron-induced chemiluminescence.Results. Prevalence of good and excellent results of treatment was registered in patients treated with Cytoflavin comparing with those placebo (56% vs. 22%; р = 0.036). Psychological examination showed more expressed positive dynamics of physic activity rate in treatment with the active preparation comparing with those placebo (972 ± 184 sec vs. 1 251 ± 449 sec; р = 0.005). In the group of patients treated with Cytoflavin IP P300 showed the increase of P300 peak amplitude (before treatment 5.2 ± 1.2 mV, after treatment 7.2 ± 2.1 mV; р = 0.035). The biochemical basis of the therapeutic action of Cytoflavin was its antioxidant activity: Cytoflavin increased the endogenous antioxidant background (before treatment 46.8 ± 16.1 sec, after treatment 62.4 ± 13.6 sec, р = 0.004).Conclusions. Cytoflavin produces positive effects on the main symptoms in patients with chronic brain ischaemia, increases endogenous antioxidant background and possesses certain neurotropic activity.

Synaptamide Modulates Astroglial Activity in Mild Traumatic Brain Injury

At present, the study of the neurotropic activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines) is becoming increasingly important. N-docosahexaenoylethanolamine (synaptamide, DHEA) is a highly active metabolite of docosahexaenoic acid (DHA) with neuroprotective, synaptogenic, neuritogenic, and anti-inflammatory properties in the nervous system. Synaptamide tested in the present study was obtained using a chemical modification of DHA isolated from squid Berryteuthis magister liver. The results of this study demonstrate the effects of synaptamide on the astroglial response to injury in the acute (1 day) and chronic (7 days) phases of mild traumatic brain injury (mTBI) development. HPLC-MS study revealed several times increase of synaptamide concentration in the cerebral cortex and serum of experimental animals after subcutaneous administration (10 mg/kg/day). Using immunohistochemistry, it was shown that synaptamide regulates the activation of GFAP- and S100β-positive astroglia, reduce nNOS-positive immunostaining, and stimulates the secretion of neurotrophin BDNF. Dynamics of superoxide dismutase production in synaptamide treatment confirm the antioxidant efficacy of the test compound. We found a decrease in TBI biomarkers such as GFAP, S100β, and IL-6 in the blood serum of synaptamide-treated experimental animals using Western blot analysis. The results indicate the high therapeutic potential of synaptamide in reducing the severity of the brain damage consequences.

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidines on the Basis of pyrano[3,4-c]pyridines.

Background: 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. Methods: 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. Results: 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 thieno[2,3-b]pyridines and tetracyclic pyridothieno[3,2-d]pyrimidin-8-ones, especially pronounced in compounds 3b–f and 4e. The studied compounds increase the latent time of first immobilization on the “forced swimming” (FS) model and exhibit antidepressant effects; compounds 3e and 3f especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds 3c and 4b bound tightly in the active site of γ-aminobutyric acid type A (GABAA) receptors with a value of the scoring function that estimates free energy of binding (∆G) at −10.0 ± 5 kcal/mol. Compound 4e showed the best affinity ((∆G) at −11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin (SERT) transporter. Compounds 3c–f and 4e practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound 3f ((∆G) at −9.3 ± 0.46 kcal/mol). Conclusions: The selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects.

Molecular Structural Features that Determine the Neurotropic Activity of Thiamine Derivatives

Molecular Structural Features that Determine the Neurotropic Activity of Thiamine Derivatives

New type of recyclization in 3,4-dihydroisoquinolines in the synthesis of β-(o-indazolylaryl)ethylamines and their 7-azaindazolyl analogues

1-(2-Hydrazinoaryl)-3,4-dihydroisoquinolines and their hydrazinopyridyl analogues undergo recyclization affording novel (7-aza)indazolyl-β-arylethylamines. The products are expected to possess neurotropic activities.

Synthesis, Neurotropic Activity, and Molecular Docking of New Condensed Thieno[2,3-b]pyridine Derivatives

Synthesis, Neurotropic Activity, and Molecular Docking of New Condensed Thieno[2,3-b]pyridine Derivatives