Glocal University is a private and coeducational institution located in Saharanpur, Uttar Pradesh, India. It is situated in the foothills of Shivalik mountains. The university is a non-profit university established by the Uttar Pradesh Private Universities Act, 2011, (U.P. Act no. 2 of 2012) and is recognized by University Grant Commission. In keeping with its vision of Global canvass, local colours, the school's name is a portmanteau of "global" and "local". The university's 6 major schools offer more than 35 undergraduate, post-graduate, and professional courses.
Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment; yet, there is currently no treatment. A buildup of Aβ, tau protein phosphorylation, oxidative stress, and inflammation in AD is pathogenic. The accumulation of amyloid-beta (Aβ) peptides in these neurocognitive areas is a significant characteristic of the disease. Therefore, inhibiting Aβ peptide aggregation has been proposed as the critical therapeutic approach for AD treatment. Resveratrol has been demonstrated in multiple studies to have a neuroprotective, anti-inflammatory, and antioxidant characteristic and the ability to minimize Aβ peptides aggregation and toxicity in the hippocampus of Alzheimer's patients, stimulating neurogenesis and inhibiting hippocampal degeneration. Furthermore, resveratrol's antioxidant effect promotes neuronal development by activating the silent information regulator-1 (SIRT1), which can protect against the detrimental effects of oxidative stress. Resveratrol-induced SIRT1 activation is becoming more crucial in developing novel therapeutic options for AD and other diseases that have neurodegenerative characteristics. This review highlighted a better knowledge of resveratrol's mechanism of action and its promising therapeutic efficacy in treating AD. We also highlighted the therapeutic potential of resveratrol as an AD therapeutic agent, which is effective against neurodegenerative disorders.
Background: Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge. Methods: Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites. Results: The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives. Conclusion: The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.
The present investigation determines the effects of rosiridin in cisplatin (CP)-induced renal toxicity in rats. The experimental animals were used and divided into four groups. Experimental rats were randomly divided into group-I normal control, group-II CP group (8 mg/kg i.p.), group-III CP + rosiridin (10 mg/kg, p.o.) and group-IV rosiridin (10 mg/kg p.o.). Various biochemical parameters, i.e., creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, inflammatory markers such as interleukins-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), apoptosis markers including B cell lymphoma-2 (Bcl-2), caspase-3 and histopathological investigations were evaluated. Additionally, molecular docking and dynamics were performed to assess the interaction of rosiridin with target proteins. Rosiridin significantly minimized alteration in creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, and inflammatory, i.e., IL-1β, IL-6, TNF-α, NF-κB, Bcl-2, and caspase-3 which CP induced in rats. The interaction of rosiridin showed a favorable docking energy. The MD simulation results showed the higher stability of the complex generated from rosiridin. The current study exhibited rosiridin having a protective effect on CP-induced renal toxicity.
Integrated farming systems (IFS) may improve soil carbon storage by diversifying biomass inputs and reducing reliance on continuous cereal cultivation. This field study assessed depth-wise soil organic carbon (SOC) stock and surface-layer carbon sequestration in a decade-old IFS model at the Farming System Research Centre, SKUAST-Jammu, Chatha, relative to an adjoining existing farmer’s farming system (EFFS) under continuous rice–wheat cultivation. Composite soil samples were collected from four depths (0–15, 15–30, 30–45 and 45–60 cm) and analysed for organic carbon using the Walkley–Black method, while bulk density was determined by the core method. Carbon stock and sequestration were calculated from SOC concentration, bulk density and soil depth, and the data were analysed using a randomised block design. Soil carbon stock decreased with increasing depth across all land uses. The highest SOC stock up to 60 cm was recorded under boundary plantation with turmeric intercropping (46.64 Mg C ha⁻¹), followed by fodder, horticulture and crop blocks, while the lowest occurred under EFFS (26.34 Mg C ha⁻¹). Overall, the IFS model accumulated 38.91 Mg C ha⁻¹ up to 60 cm, representing about 48% greater carbon storage than in EFFS. Surface-layer carbon sequestration ranged from 2.94 Mg C ha⁻¹ under perennial fodder to 7.90 Mg C ha⁻¹ under boundary plantation, whereas EFFS showed a negative value (–0.65 Mg C ha⁻¹). Over ten years, the IFS model achieved an overall carbon sequestration of 4.47 Mg C ha⁻¹, demonstrating its greater potential for soil carbon accumulation compared with continuous rice–wheat cultivation.
Objective: This work aimed to design, synthesize, and biologically evaluate a novel series of fused benzoxazole-imidazo[1,2-c][1,2,3]triazole derivatives. Methods: The target compounds Va–Vo were synthesized via a one-pot, copper-catalyzed cyclization in polyethylene glycol-400 (PEG-400). Their in vitro cytotoxicity was evaluated against the human breast adenocarcinoma cell lines MCF-7 and MDA-MB-231 using the MTT assay. Erlotinib was used as the reference inhibitor. The most active compounds were subjected to molecular docking studies against the epidermal growth factor receptor (EGFR) kinase domain (PDB ID: 4HJO) to elucidate their potential binding mode. Results and Discussion: All synthesized derivatives were characterized by ESI-HRMS, 1H, and 13C NMR spectroscopy. Compounds Vf, Vh, Vk, and Vl displayed significant cytotoxic activity with IC50 values ranging from 4.28 ± 0.53 to 7.44 ± 0.72 µM against both cancer cell lines, showing potency superior to that of erlotinib (IC50 = 4.68– 7.29 µM). Furthermore, these compounds exhibited markedly reduced cytotoxicity towards the non-tumorigenic mammary epithelial cell line MCF-10A, indicating a selective anticancer profile. Docking simulations revealed that the active compounds favorably bind to the EGFR ATP-binding site, with calculated free energies of binding ranging from –9.13 to –8.36 kcal/mol, which correlate with their in vitro potency and exceed the docking score of erlotinib (–7.69 kcal/mol). Conclusions: A new class of benzoxazole-imidazotriazole hybrids was successfully developed using an eco-friendly synthetic protocol. Several derivatives demonstrated potent and selective anticancer activity against breast cancer cell lines, likely mediated through EGFR inhibition, as supported by computational studies. Derivative Vk, with the highest activity and selectivity, is identified as a promising lead for further development.
