N-Substituted 2-(Benzenosulfonyl)-1-Carbotioamide Derivatives Exert Antimicrobial and Cytotoxic Effects via Aldehyde Dehydrogenase Pathway: Synthesis, In Silico and In Vitro Studies.

A series of N-Substituted 2-(benzenosulfonyl)-1-carbotioamide derivatives (WZ1-WZ4) were synthesized and characterized using spectral methods. A comprehensive activity study was performed for each compound. All compounds were tested for antibacterial activity. Moreover, in silico studies were carried out to determine the anticancer potential of the designed WZ1-WZ4 ligands. Based on molecular docking, aldehyde dehydrogenase was selected as a molecular target. The obtained data were compared with experimental data in vitro tests. Novel hybrids of the thiosemicarbazide scaffold and sulfonyl groups may have promising anticancer activity via the aldehyde dehydrogenase pathway. The best candidate for further studies appears to be WZ2, due to its superior selectivity in comparison to the other tested compounds.

Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety.

Twenty-five years have passed since the discovery of the orexin system, during which time we have learned more and more about it. A number of studies have been conducted showing the role of the orexin system in insomnia, as well as its potential use in the treatment of obesity and depression. In this review, we present the role of the orexin system in the development of depressive illness and show the characteristics of seltorexant, a potential drug for the treatment of depression. This review describes the structure and synthesis of the compound as well as its pharmacodynamics and pharmacokinetics. Pre-clinical and clinical studies are also described, including side effects. There is evidence that the use of seltorexant is considered safe, with no clear or major clinically significant side effects, which makes it a promising candidate for the treatment of depression and anxiety disorders.

The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases.

Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer's disease (AD), Parkinson's Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Presented data shows that consuming a diet abundant in fruits, vegetables, nuts, herbs, spices, and legumes that are sources of anti-inflammatory elements such as omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics while avoiding foods that promote inflammation, create a positive brain environment and is associated with a reduced risk of neurological diseases. Personalized nutritional interventions may constitute a non-invasive and effective strategy in combating neurological disorders.

Recent Studies on the Development of Nicotine Abuse and Behavioral Changes Induced by Chronic Stress Depending on Gender.

Nowadays, stressful situations are an unavoidable element of everyday life. Stressors activate a number of complex mental and physiological reactions in the organism, thus affecting the state of health of an individual. Stress is the main risk factor in the development of mental disorders, such as depression and other disorders developing as a result of addiction. Studies indicate that women are twice as likely as men to develop anxiety, depression and therefore addiction, e.g., to nicotine. Even though the data presented is indicative of significant differences between the sexes in the prevalence of these disorders, the majority of preclinical animal models for investigating stress-induced disorders use predominantly male subjects. However, the recent data indicates that this type of studies has also been launched in female rodents. Therefore, conducting research on both sexes allows for a more accurate understanding and assessment of the impact of stress on stress-induced behavioral, peripheral and molecular changes in the body and brain. In this manuscript we have gathered the data from 41 years (from 1981-2022) on the influence of stress on the development of depression and nicotine addiction in both sexes.

A Comprehensive Review of Daridorexant, a Dual-Orexin Receptor Antagonist as New Approach for the Treatment of Insomnia.

Insomnia affects 4.4-4.8% of the world's population, but because the effect of hypnotic drugs is limited and may cause harmful side-effects, scientists are turning their attention to developing drugs that act on the orexin system. Daridorexant, a selective dual-orexin receptor antagonist (DORA), has exhibited promising results in both animal and human studies. Its activity was evaluated based on the physiology-based pharmacodynamic and pharmacokinetic model. The use of daridorexant is considered safe, with no clinically significant side-effects including deprivation of next-morning residual effects. In this manuscript we conducted a comprehensive review of daridorexant including pharmacodynamics, animal and human research, pharmacokinetics and safety.

Cebranopadol as a Novel Promising Agent for the Treatment of Pain.

Opioids are used to treat pain, but despite their effectiveness, they possess several side effects such as respiratory depression, tolerance and physical dependence. Cebranopadol has been evaluated as a solution to this problem. The compound acts on the mu opioid receptor and the nociceptin/orphanin receptor and these receptors co-activation can reduce opioid side-effects without compromising analgesia. In the present review, we have compiled information on the effects of cebranopadol, its pharmacokinetics, and clinical trials involving cebranopadol, to further explore its promise in pain management.

The Occurrence and Biological Activity of Tormentic Acid-A Review.

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3ß,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.