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Hepatotoxicity, a critical liver damage often caused by drugs like paracetamol (PCM), involves oxidative stress, inflammation, and cellular injury. This study investigates the hepatoprotective potential of a benzimidazole-pyrazole derivative, 2-((1H-benzo[d]imidazol-2-yl) thio)-1-(3-(2-fluorophenyl)-5-phenyl-1H-pyrazol-1-yl) ethanone (M3F), using both in silico and in vivo approaches. Pharmacokinetic profiling was performed using SwissADME and ProTox to predict drug-likeness and toxicity. Molecular docking studies were conducted using AutoDock Vina integrated with PyRx to evaluate the binding affinity of M3F with key targets related to oxidative stress and inflammation. Subsequently, in vivo studies were conducted using a PCM-induced hepatotoxicity model in mice, wherein M3F was administered orally at doses of 100, 200, and 400 µg/kg for seven consecutive days, followed by a single dose of PCM (300 mg/kg, intraperitoneally) on the eighth day to induce liver injury. Serum markers of liver damage, lipid profiling, antioxidant assays, histopathological examinations and molecular markers analysis were performed to determine the therapeutic effects of M3F. In silico analysis revealed favorable pharmacokinetic properties and strong binding affinities of M3F to inflammatory and oxidative stress-related molecular targets. In vivo, M3F treatment led to a marked improvement in liver enzyme levels and lipid profiles, along with significant histological recovery of liver tissue. The study demonstrated a significant downregulation of IL-6, IL-1β, and TNF-α protein levels, as measured by ELISA, indicating reduced inflammatory responses following M3F treatment. Additionally, PCR analysis revealed a notable decrease in the mRNA expression levels of IL-17, NF-κB, and TLR4, alongside an increase in Nrf2 and HO-1 transcript levels. It is suggested that M3F demonstrated notable hepatoprotective effects in PCM-induced liver injury through dual modulation of inflammatory (NF-κB) and antioxidant (Nrf2) pathways. These findings support its potential as a novel hepatoprotective candidate for future studies.

Diabetes mellitus remains a global health challenge, necessitating the development of novel therapeutic agents. In this study, a series of thiohydantoin derivatives (FP1–FP7) were synthesized and evaluated for their in silico, in vitro, and in vivo antidiabetic potential. Molecular docking studies revealed strong binding affinities of derivatives towards α-glucosidase (PDB: 3wy1) and α-amylase (PDB: 3dhp), with FP4 exhibiting the most favorable interactions (− 7.8 kcal/mol with α-amylase and − 7.0 kcal/mol with α-glucosidase), involving hydrogen bonding and π-π stacking. During in vitro enzyme inhibition assay, FP4 demonstrated potent inhibitory activity against α-glucosidase and α-amylase, with IC₅₀ values of 129.40 and 128.90 µg/mL, respectively. The DPPH scavenging assay also indicated that FP4 had relatively strong antioxidant activity, with an IC₅₀ value of 39.7 µg/mL. In vivo antidiabetic efficacy was evaluated in STZ-induced diabetic rats over a period of 6-week. FP4 treated diabetic rats exhibited significantly reduced fasting blood glucose by 28.9% than in diabetic controls. In addition, HbA1C levels and diabetes-associated weight loss were significantly curtailed in these animals than untreated diabetic group. Further FP4 treated animals exhibited significantly decreased LDL and triglyceride levels and elevated HDL levels, suggesting a broader metabolic benefit. Taken together, our results suggest that thiohydantoin derivatives, particularly FP4, exhibited interesting antidiabetic and antihyperlipidemic activities warranting further pharmacokinetic and mechanistic investigations also potential for clinical translation and long term safety assessment.

Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (1H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-α), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.

Benzothiazoles (BTZ) possess various medicinal benefits and in this study, we have synthesized benzothiazole derivatives by substituting its side chains, and analyzed its spectral analysis along with its antioxidant and anti-inflammatory activity. In-vitro antioxidant activity of the benzothiazole derivatives indicated strong antioxidant potential of 3b , 3d and 3e which were then evaluated for their anti-inflammatory potential in mice’s paw edema and ethanol-induced gastric ulcer (GU). The compounds demonstrated strong anti-inflammatory ability in paw edema as well as ethanol-induced gastric ulcer. This was further confirmed by H&E staining and suppressed inflammatory mediators as tumor necrotic factor (TNF-α), nuclear factor B (p-NFkB), and cyclooxygenase-2 (COX-2). The antioxidant ability was assessed by measuring catalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels in both edema and ulcer models. Additionally, gastric lesions were detected in the ulcer and low Ulcer index confirmed anti-ulcer ability. These results suggest new benzothiazoles which can be further analyzed through clinical studies.

Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski’s rule of five. 5b showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 μg/mL concentration. Compounds showed antibacterial activity against various tested strains. 5e and 5f showed a minimum inhibitory concentration (MIC) value of 3.12 μg/mL for P.aeruginosa and K . pneumoniae , respectively. In the antifungal assay, only 5e inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; 5c, 5d, and 5f exhibited LC 50 = 5.7 μg/mL. In the protein kinase inhibition assay, 5a, 5b, and 5g demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5–10.5 mm for the bald one and 6–7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area.

Isoxazole derivatives are significant enough due to their wide range of pharmacological and therapeutic activities. The purpose of the current study is to use computational, in vitro, in vivo, and extensive molecular approaches to examine the possible anti-ulcer activity of 4-benzylidene-3 methyl-1,2-isoxazol-5(4H)-one (MBO). Biovia Discovery Studio visualizer (DSV) was utilized for virtual screening. A tissue antioxidant investigation, H+/K+-ATPase test, and anti-H. pylori activities were carried out. ELISA, immunohistochemistry, and PCR methods were employed for the proteome analysis. An ethanol-induced stomach ulcer model was used to examine the anti-ulcer potential in rats. The binding affinities for MBO ranged from −5.4 to −8.2 Kcal/mol. In vitro findings revealed inhibitory activity against H. pylori and the H+/K+-ATPase pump. It also enhanced levels of glutathione, catalase, and glutathione-S-transferase and reduced lipid peroxidation levels in gastric tissues of rats. In vivo results showed the gastro-protective effect of MBO (30 mg/kg) in ulcerative rat stomachs. The proteomic study revealed decreased expression of inflammatory markers (cyclooxygenase-2, p-NFkB, and TNF-α). In RT-PCR analysis, the expression levels of H+/K+-ATPase were reduced. Furthermore, ADMET (absorption, distribution, metabolism, excretion and toxicity) studies revealed that MBO has high GIT solubility and has a safer profile for cardiac toxicity. This study suggests that MBO displayed anti-ulcer potential, which may have been mediated through the inhibition of the H+/K+-ATPase pump, as well as antioxidant and anti-inflammatory pathways. It has the potential to be a lead molecule in the treatment of peptic ulcers with fewer adverse effects.

Alzheimer's disease (AD) is age-dependent neurological disorder with progressive loss of cognition and memory. This multifactorial disease is characterized by intracellular neurofibrillary tangles, beta amyloid plaques, neuroinflammation, and increased oxidative stress. The increased cellular manifestations of these markers play a critical role in neurodegeneration and pathogenesis of AD. Therefore, reducing neurodegeneration by decreasing one or more of these markers may provide a potential therapeutic roadmap for the treatment of AD. AD causes a devastating loss of cognition with no conclusive and effective treatment. Many synthetic compound containing isoxazolone nucleus have been reported as neuroprotective agents. The aim of this study was to explore the anti-Alzheimer’s potential of a newly synthesized 3,4,5-trimethoxy isoxazolone derivative (TMI) that attenuated the beta amyloid (Aβ1-42) and tau protein levels in streptozotocin (STZ) induced Alzheimer’s disease mouse model. Molecular analysis revealed increased beta amyloid (Aβ1-42) protein levels, increased tau protein levels, increased cellular oxidative stress and reduced antioxidant enzymes in STZ exposed mice brains. Furthermore, ELISA and PCR were used to validate the expression of Aβ1-42. Pre-treatment with TMI significantly improved the memory and cognitive behavior along with ameliorated levels of Aβ1-42 proteins. TMI treated mice further showed marked increase in GSH, CAT, SOD levels while decreased levels of acetylcholinesterase inhibitors (AChEI’s) and MDA intermediate. The multidimensional nature of isoxazolone derivatives and its versatile affinity towards various targets highpoint its multistep targeting nature. These results indicated the neuroprotective potential of TMI which may be considered for the treatment of neurodegenerative disease specifically in AD.

A series of six novel benzimidazole-pyrazole hybrid molecules was synthesized and characterized using elemental analysis (CHN) and spectroscopic methods (1HNMR, FT-IR). All the synthesized compounds were evaluated for their in vivo anti ulcerogenic activity using Albino rats (weighing 180–220 g). The interactions between the compounds and active site residues of H+/K+ ATPase were investigated by molecular docking studies using autodock vina 4.0. SCH28080 was used to validate the docking results. Also the drug likeliness of these compounds was predicted using Molinspiration server in light of Lipinski’s rule of five. All the six synthesized compounds exhibited higher anti-ulcer activity as compared to omeprazole. These novel hybrid compounds showed comparable anti-ulcer potential of 72–83% at dose level of 500 µg/kg, whereas omeprazole showed 83% anti-ulcer activity at dose level of 30 mg/kg. The results clearly indicate that these novel benzimidazole-pyrazole hybrids can present a new class of potential anti ulcer agents and can serve as new anti-ulcer drugs after further investigation.[Figure not available: see fulltext.]

Rosa webbiana L. (Rosaceae) is one of the least reported and most understudied members of this family. It is native to the Himalayan regions of Pakistan and Nepal. The anti-convulsant effect of n-hexane extract of fruit of Rosa webbiana was investigated in a pentylenetetrazole (PTZ)-induced animal model of epilepsy. Male Sprague-Dawley rats were divided into six groups (n = 7) including control, PTZ (40 mg/kg), diazepam (4 mg/kg) and n-hexane extract (at 50, 150 and 300 mg/kg). Convulsive behavior was observed and resultant seizures were scored, animals sacrificed and their brains preserved. Chitosan nanoparticles were prepared using the ionic gelation method and characterized by UV-analysis, zeta potential and Fourier transform infrared spectroscopy (FTIR). The effects of all the treatments on the expression of phosphorylated cytokine tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) expression in the cortex and hippocampus of the brains of treated rats were studied through enzyme linked immunosorbent assay (ELISA) and morphological differences and surviving neuronal number were recorded through hematoxylene and eosin (H&E) staining. Significant changes in seizures score and survival rate of rats were observed. Downregulation of neuro-inflammation, p-TNF-α and p-NF-κB was evident. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of this fraction showed multiple constituents of interest, including esters, alkanes and amines.

The present study aims to investigate the newly synthesized organotin (IV) complex (2E, 2′E) dibutylstannanediyl bis (4-(4-nitrophenyl) amino)-4-oxobut-2-enoate (DTN) for its anti-ulcer potential. Characterization performed by carbon nuclear magnetic resonance spectroscopy proved that all values are in the expected ranges of the new compound. Gastroprotective activity of DTN was evaluated through in-silico, anti- H. pylori, in-vitro , in-vivo, and ex-vivo proteomic analysis. In-silico analysis shows that DTN possess stable binding with protein targets involved in gastric ulcer pathophysiology. DTN exhibited an inhibitory effect against 2,2-diphenyl-1-picrylhydrazyl, H. pylori and hydrogen potassium ATPase (H + /K + -ATPase). The antiulcer activity was performed using an ethanol-induced gastric ulcer model in rats. Anti-oxidant profile of DTN showed a significant increase in glutathione-S-transferase, glutathione and catalase levels whereas lipid peroxidation levels were reduced. Histopathological findings confirmed that DTN protected the gastric mucosa of rats. Inflammatory markers tumor necrosis factor-alpha, nuclear factor kappa B, cyclooxygenase-2, interleukin 6 and interleukin-1β were reduced and prostaglandin-E 2 restored expression of these cytokines in DTN pretreated animals when analyzed by using immunohistochemistry, enzyme-linked immunosorbent assay and western blot techniques. In real-time polymerase chain reaction technique, the expression of H + /K + -ATPase was downregulated in DTN pretreated group. DTN did not cause any mortality up to 400 mg/Kg. This study indicates that the newly synthesized compound DTN, possess stable binding against selected targets. DTN exhibits a gastro-protective effect, mediated via anti- H. pylori, H + /K + -ATPase inhibition, anti-oxidant and anti-inflammatory pathways, exploring its therapeutic potential in gastric ulcer management.