Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Current Issue

Tuberculosis (TB) is the most common disease that affects the lungs, and it is associated with Mycobacterium tuberculosis infection. Many synthetic medications, such as pyrazinamide, isoniazid, and ethambutol, are available to treat TB; however, their adverse effects are severe. Medicinal herbs have lately become popular, safe, and effective alternative treatments for TB.

The purpose of this systematic review was to assess the possible use of natural plants in the development of herbal treatments and remedies for TB by studying the medicinal plants and phytochemicals that have been used for the disease. Information was gathered from a variety of sources, including Bentham, Elsevier, Springer, Nature, Google Scholar, PubMed, Sci-Finder, and the Web of Science. For the investigation, common and scientific names of plants, as well as terms like “mycobacterium tuberculosis,” “herbal plants,” “flavonoids,” and “alkaloids” were employed. In the end, 376 plants belonging to 83 families were discovered, and details about each plant family, as well as the section of the plant utilized, chemical components, extract, and strain, were extracted.

The findings showed that although flavonoids and alkaloids were the most prevalent naturally occurring substances found in plants, the Fabiaceae family had a greater potential to eradicate TB.

The leaf portion was shown to be more active, and the S-37 RV strain of Mycobacterium TB was employed more frequently.

We aimed to conduct in silico screening of the potential phytoconstituent from a natural product database to find SIRT2 inhibitors.

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by behavioral and mental symptoms as well as a progressive loss of cognitive ability. Since SIRT2 may be detrimental to neurological illnesses, it is a prime target for research into SIRT2 inhibitors.

To identify the SIRT2 inhibitors and their role in AD.

We have utilized NPAtlas database and screened using pharmacophore-based virtual screening, molecular docking, and simulation. The Natural Products Atlas provides unrestricted access to various natural products derived from bacteria and fungi, allowing researchers to investigate and visualize the extensive chemical diversity in the natural world.

From in silico screening data, we have found phytoconstituents that could function as SIRT2 inhibitors. Six phytoconstituents were identified using pharmacophore-based virtual screening. According to molecular docking, Kurasoin B outperformed the reference molecule regarding binding energy. Kurasoin B exhibited a binding affinity of -12.543 kcal/mol, whereas the binding affinity of the reference molecule was -12.089 kcal/mol. The Kurasoin B complex with SIRT2 was determined to be stable throughout the simulation by performing MD simulation, with an RMSD of 2.88 (Å), whereas the reference and free protein displayed RMSDs of 3.74 and 4.70 (Å), respectively.

In silico studies and data analysis, suggest that Kurasoin B may be able to suppress the SIRT2 protein for managing AD.

Epilepsy is a critically deep-rooted CNS disorder affecting above 50 million people all over the world. Thus, a safe and effective treatment that proves its worth in this ailment is urgently needed. Thiazolidine-4-ones possess the molecules to be used as anticonvulsants. The thiazolidinedione is a cyclic analogue of thiosemicarbazides and thioureas as well as a (bio)isostere of hydantoin (imidazolidine-2,4-dione), which are recognized as novel anticonvulsant designs.

This study aimed to develop and evaluate a novel thiazolidine-4-one derivative by three-component condensation in one pot reaction method.

A novel thiazolidine-4-one derivative was formulated by three-component condensation. The selected OH (Alcohol) derivatives were found to be more potent; hence, a molecular docking study against a selected target LGI1 LRR domain was performed. Various analytical tests like FTIR and H¹ NMR were accomplished. The FTIR was used to validate the existence of multiple functional moieties like C-S, O-H, C=O, C-N, N=O, C-NH, C-O in the wave region from 3075 cm^-1 – 1236 cm^-1 and H¹ NMR was employed to ascertain if the synthesized analogues had the complete set of protons. Then, the anti-seizure activity of the selected compound was examined using PTZ models in mice at three successive doses, i.e., 25, 50, and 100mg/kg, and compared with standard ethosuximide.

The docking simulations were initiated using PyMOL after the binding site was determined and the receptor and ligand were suitably prepared. It showed higher binding frequency in comparison to the standard marketed drug Ethosuximide. FTIR and H¹ NMR spectroscopy were used to characterize the chemical components. Numerous functional groups, including O-H (alcohol), C=O (ketones), N=O, C-NH, C-N, C-S, and C-O bending stretching, were visible in the synthesized molecule accordingly. The synthesized compound was effective in inhibiting the convulsions at the concentration of 100 mg/kg.

The novel thiazolidine-4-one derivative showed promising activity and could be considered for further investigation and dosage form preparation.

This study aims to investigate the antidepressant properties of Hispidulin, a flavonoid present in Scutellaria barbata D. Don. The selection of Hispidulin stems from its notable inhibitory activity against Xanthine Oxidase (XO), a parameter in the pathophysiology of depression.

Mice were subjected to a rigorous evaluation using a murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression for 21 days and antidepressant properties were rigorously assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Imipramine and fluoxetine were used as standard drugs. Additionally, neurochemical analyses were conducted to quantify serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels in the cortex, hippocampus, and hypothalamus. Further mechanistic insights were sought through the estimation of monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in the brain. Plasma nitrite and corticosterone levels were also measured to delineate the underlying mechanism of action.

Hispidulin demonstrated significant antidepressant effects, as evidenced by reduced immobility time in TST and FST and increased exploratory behavior in OFT. Neurochemical analysis revealed restoration of 5-HT, NE, and DA levels in key brain regions. Furthermore, Hispidulin modulated MAO activity and enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were elevated, indicating enhanced nitric oxide synthesis, while corticosterone levels were reduced.

Our findings indicate that Hispidulin exerts potent antidepressant effects, potentially mediated through its influence on monoaminergic neurotransmitters, MAO activity, and antioxidant defenses. These results provide valuable mechanistic insights into the antidepressant action of Hispidulin, supporting its potential therapeutic application in depressive disorders.

Camellia sinensis has an extensive variety of pharmacological properties, including neuroprotection, photo-aging resistance, stress resistance, antioxidant, anti-tumour, hypoglycemic, antibacterial, and antiviral effects tracing a good potential in addressing illness and preventing disease. Challenges with conventional dosage forms include patient incompatibility, improper dosing, the inclusion of microplastics, etc.

The present work aims to deliver a novel formulation devoid of microplastics and with improved consumer compliance.

Wet granulation was used to formulate 500 mg Camellia sinensis effervescent tablets, with improved effervescent time and rapid release. Citric acid and sodium bicarbonate's impacts on disintegration time and pH were examined using a factorial design. Pre-compression variables were assessed for the granule mixture. Post-compression criteria were employed to assess effervescent tablets. The optimum formulation was selected using a central composite response surface and assessment criteria.

The physicochemical characteristics of the developed formulations were significantly influenced by the independent factors. Low concentrations of sodium bicarbonate have positive impact on pH whereas high concentrations of sodium bicarbonate as well as citric acid enhance disintegration time. The design outcomes showed that the optimized effervescent tablets (F10) prepared with 697.5 mg and 448.38 mg of citric acid and sodium bicarbonate respectively had good physicochemical properties.

In compliance with present quality standards, factorial design was efficiently utilized for the development of Camellia sinensis effervescent tablets. It was concluded that green tea effervescent tablet (F10) would function as a substitute for conventional green tea powder along with green tea bags as a means of administration.

In an alternative medicinal system, Cuprum metallicum (CM) is used for the management of seizure-like conditions. However, there is a lack of scientific evidence regarding its effect.

The present study aimed to evaluate the effect of CM against Pentylenetetrazole-induced seizures in zebrafish and mice.

Zebrafish were exposed to CM-6C, CM-30C, and valproic acid for 1 Hr then fish were exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C, CM-30C, and valproic acid for 10 days. After 30 min of the last dose, pentylenetetrazole was administered intraperitoneally. Observations during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ), tonic-clonic seizures, and the severity of seizure and survival protection after 24 Hrs.

PTZ exposure significantly decreased the latency from score-1 to score-5, which CM-6C and 30C significantly increased. Furthermore, CM-6C and 30C normalized the locomotor activity affected by PTZ exposure. Among the animals treated with the CM-6C and 30C, significantly increased latency to FMJ, tonic-clonic seizures, and survival protection compared to the PTZ group of Cuprum met.

The results of the study indicate that CM 6C and 30C have the potential to work against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the treatment of epilepsy.

More than 15% of women develop symptoms of depression during pregnancy, which often affects the mental and physical development of the newborn by altering its intestinal microbiota. Previous studies revealed that the gut microbiota plays a crucial role in the maturation of systems involved in the gut-brain axis, including the gastrointestinal system, the immune system, and the hypothalamic-pituitary-adrenal system axis.

This study aims to explore the cross-talk between the prenatal depression process and neonatal intestinal microbiota diversity. A total of 100 differentially expressed genes (DEGs) associated with prenatal depression were collected from various scientific publications and databases. Bioinformatics tools were used to analyze these DEGs. The STRING database. ToppGene database and DICE were employed for this integrative analysis.

The network generated by the STRING database identified six pivotal genes: TNF, BDNF, IL-6, NR3C1, IGF2, and POMC. These genes regulate response to endogenous hormones, particularly cortisol secretion in newborns, as well as inhibiting serotonin secretion. Moreover, these genes are linked to major depressive disorder and other mental diseases, contributing to maternal and neonatal gut microbiota dysbiosis. Analysis using ToppGene and DICE’s further validated the biological processes identified by String, including the regulation of cellular cortisol secretion, metabolic processes, and serotonin inhibition.

The bioinformatics tools employed in this study allowed us to identify pivotal genes involved in prenatal depression, their associated signaling pathways, and their roles in modulating maternal and neonatal gut microbiota.