RESUMO
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.
RESUMO
The widespread use of silver nanoparticles (AgNPs) requires a study of their safety. The aim of the present study was to assess the levels of oxidative stress markers and histopathological changes in the experimental model of sarcoma S-180 of outbred mice caused by biogenic AgNPs. AgNPs were synthesized using 50% ethanol extract of Ocimum araratum leaves that was standardized for rosmarinic acid content. The effects of AgNPs were tested on chemiluminescence (ChL), malonic dialdehyde (MDA) content and activity of superoxide dismutase (SOD) in healthy and experimental model of sarcoma S-180 mice. It was shown that, under the influence of AgNPs, the intensity of ChL decreased, in contrast with control groups (with the exception of the hepatocytes of animals with transplanted sarcoma). The presence of AgNPs leads to the decrease of MDA in the tissues of healthy mice and to a slight increase of MDA content in the tumour and kidney tissues. AgNPs neutralize the activity of SOD in kidney tissue samples in animals with transplanted sarcoma, and in tumour tissue, they reduce SOD activity by three times. The results of the histological analysis indicate that AgNPs not only cause the destruction of tumour tissue but also lead to structural changes in hepatocytes and nephrons, which can affect the function of these organs. AgNPs are potential agents for antitumor therapy. Future studies are needed using biocompatible non-toxic NPs that meet the requirement for these drugs.