Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Designing and Synthesis of Novel Fexofenadine-Derived Hydrazone-Schiff bases as Potential Urease Inhibitors: In-Vitro, Molecular Docking and DFT Investigations.

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50 = 10.19 ± 0.16 µM), 11 (IC50 = 15.05 ± 1.11 µM), 10 (IC50 = 17.01 ± 1.23 µM), 9 (IC50 = 17.22 ± 0.81 µM), 13 (IC50 = 19.31 ± 0.18 µM), and 14 (IC50 = 19.62 ± 0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50 = 21.14 ± 0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

A GIS approach for groundwater quality evaluation with entropy method and fluoride exposure with health risk assessment.

This study used the entropy water quality index to analyse the suitability of groundwater for human consumption as well as the hazard index to identify the probable non-carcinogenic dangers among children, women, and men in Nawada, Bihar (India). A total of 75 groundwater samples were taken from hand pumps and tube/bore wells in the pre-monsoon of 2017, and they were evaluated for various physicochemical characteristics. The region's groundwater major cations and anions are dominated by Ca2+ > Mg2+ and [Formula: see text] > Cl- > [Formula: see text] > NO3- > F > [Formula: see text]. Fluoride, chloride, and hardness exceeded WHO and BIS safe standards. Calcium, sodium, magnesium, sulphate, and chloride showed positive correlations, indicating water-rock interactions and mineral leaching and dissolution. Ionic cross-plots reveal that the dissolution of carbonate minerals was the primary source of calcium and magnesium in the groundwater. Also, silicate weathering contributed to these ions in the groundwater. The entropy water quality index (EWQI) found that 79% of groundwater samples were drinkable, whereas 21% were not consumable. The eastern, western, and some southern study areas have the worst drinking water quality. The main source of fluoride toxicity in people is groundwater. For all sampling locations, the HQ fluoride was calculated to be in the ranges of 0.04-3.69 (male), 0.04-3.27 (female), and 0.05-4 (children), indicating a considerably greater risk than the permissible levels (> 1). The fluoride-based non-carcinogenic risks are 27%, 20%, and 21% for children, women, and men, respectively. Children have higher risks from polluted water than adults, according to the non-carcinogenic health risk assessment. This study establishes a standard for regional and global scientific studies that help decision-makers and planners determine the quality of groundwater and fluoride risk and management.

Neuroprotective potential of Afzelin: A novel approach for alleviating catalepsy and modulating Bcl-2 expression in Parkinson's disease therapy.

The lost dopaminergic neurons in the brain prevent mobility in Parkinson's disease (PD). It is impossible to stop the disease's progress by means of symptoms management. Research focuses on oxidative stress, mitochondrial dysfunction, and neuronal degeneration. Exploration of potential neuroprotective drugs against prosurvival B-cell lymphoma 2 (Bcl-2) protein is ongoing. An investigable cause behind PD, as well as preventive measures, could be discovered considering the association between such behavioural manifestations (cataleptic behaviours) and PD. The compound Afzelin, known to guard the nervous system, was chosen for this study. The study was done on rats divided into six different groups. First, there was a control group. The other group was treated with Reserpine (RES) (1 mg/kg). The third group received RES (1 mg/kg) and levodopa (30 mg/kg). The remaining three groups were given RES (1 mg/kg) in conjunction with Afzelin at the following doses: 5 mg/kg, 10 mg/kg, and 20 mg/kg. Cataleptic behavior and mobility in rats was assessed using the rotarod, open field, and modified forced-swim tests. thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), biogenic amines, and Bcl-2 level in rat tissue homogenates were considered. According to the study's findings, the rats treated through co-administration of RES and Afzelin improved significantly in their cataleptic behaviours and locomotor activity. In addition, administering Afzelin itself caused Bcl-2 expression, which could have some neuroprotection properties. This study provides meaningful information on the effectiveness of Afzelin in handling catalepsy and other degenerative neurologic disorders. As a result, other studies need to be conducted to establish the reasons behind the reactions and determine the long-term effects of Afzelin on these conditions.

Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies.

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.

Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach.

The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

Astrocytes display cell autonomous and diverse early reactive states in familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis remain unresolved. Here we systematically examine these issues by using highly enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations. We show that VCP mutant astrocytes undergo cell-autonomous reactive transformation characterized by increased expression of complement component 3 (C3) in addition to several characteristic gene expression changes. We then demonstrate that isochronic SOD1 mutant astrocytes also undergo a cell-autonomous reactive transformation, but that this is molecularly distinct from VCP mutant astrocytes. This is shown through transcriptome-wide analyses, identifying divergent gene expression profiles and activation of different key transcription factors in SOD1 and VCP mutant human induced pluripotent stem cell-derived astrocytes. Finally, we show functional differences in the basal cytokine secretome between VCP and SOD1 mutant human induced pluripotent stem cell-derived astrocytes. Our data therefore reveal that reactive transformation can occur cell autonomously in human amyotrophic lateral sclerosis astrocytes and with a striking degree of early molecular and functional heterogeneity when comparing different disease-causing mutations. These insights may be important when considering astrocyte reactivity as a putative therapeutic target in familial amyotrophic lateral sclerosis.

Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking.

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.

Oxygen and moisture-induced healing of halide double perovskite surface defects.

In this work, we studied the impact of environmental constituents such as oxygen (O2) and moisture on halide double perovskite (HDP) films. The transport measurements indicate that an increment in O2 concentration enhances the resistivity of a Cs2AgBiBr6 film by two orders of magnitude. The adsorption of O2 on the film's surface helps in passivation of defects (∼50% reduction in defect density on O2 exposure), which inhibits ion migration and results in an increased resistivity of the film. The process of adsorption and desorption of O2 on the film surface is found to be fully reversible. In contrast, the resistivity of double perovskite films decreases by an order of magnitude in the presence of moisture. This is attributed to the generation of free protons as a result of the dissociation of water molecules at the films' surface, hence exhibiting an increase in current under external bias. The HDP films possess high resistivity (for T < 100 °C) due to the desorption of physisorbed water layers from the surface, which gradually decreases with an increase in the operating temperature. This work demonstrates that O2 and moisture are a good combination for defect passivation in any HDPs, in general.

Human Action Recognition: A Taxonomy-Based Survey, Updates, and Opportunities.

Human action recognition systems use data collected from a wide range of sensors to accurately identify and interpret human actions. One of the most challenging issues for computer vision is the automatic and precise identification of human activities. A significant increase in feature learning-based representations for action recognition has emerged in recent years, due to the widespread use of deep learning-based features. This study presents an in-depth analysis of human activity recognition that investigates recent developments in computer vision. Augmented reality, human-computer interaction, cybersecurity, home monitoring, and surveillance cameras are all examples of computer vision applications that often go in conjunction with human action detection. We give a taxonomy-based, rigorous study of human activity recognition techniques, discussing the best ways to acquire human action features, derived using RGB and depth data, as well as the latest research on deep learning and hand-crafted techniques. We also explain a generic architecture to recognize human actions in the real world and its current prominent research topic. At long last, we are able to offer some study analysis concepts and proposals for academics. In-depth researchers of human action recognition will find this review an effective tool.

QbD-Optimized, Phospholipid-Based Elastic Nanovesicles for the Effective Delivery of 6-Gingerol: A Promising Topical Option for Pain-Related Disorders.

In this study, elastic nanovesicles, constructed of phospholipids optimized by Quality by Design (QbD), release 6-gingerol (6-G), a natural chemical that may alleviate osteoporosis and musculoskeletal-related pain. A 6-gingerol-loaded transfersome (6-GTF) formulation was developed using a thin film and sonication approach. 6-GTFs were optimized using BBD. Vesicle size, PDI, zeta potential, TEM, in vitro drug release, and antioxidant activity were evaluated for the 6-GTF formulation. The optimized 6-GTF formulation had a 160.42 nm vesicle size, a 0.259 PDI, and a -32.12 mV zeta potential. TEM showed sphericity. The 6-GTF formulation's in vitro drug release was 69.21%, compared to 47.71% for the pure drug suspension. The Higuchi model best described 6-G release from transfersomes, while the Korsmeyer-Peppas model supported non-Fickian diffusion. 6-GTF had more antioxidant activity than the pure 6-G suspension. The optimized transfersome formulation was converted into a gel to improve skin retention and efficacy. The optimized gel had a spreadability of 13.46 ± 4.42 g·cm/s and an extrudability of 15.19 ± 2.01 g/cm2. The suspension gel had a 1.5 µg/cm2/h ex vivo skin penetration flux, while the 6-GTF gel had 2.71 µg/cm2/h. Rhodamine B-loaded TF gel reached deeper skin layers (25 µm) compared to the control solution in the CLSM study. The gel formulation's pH, drug concentration, and texture were assessed. This study developed QbD-optimized 6-gingerol-loaded transfersomes. 6-GTF gel improved skin absorption, drug release, and antioxidant activity. These results show that the 6-GTF gel formulation has the ability to treat pain-related illnesses effectively. Hence, this study offers a possible topical treatment for conditions connected to pain.

The Cardioprotective Effect of Corosolic Acid in the Diabetic Rats: A Possible Mechanism of the PPAR-γ Pathway.

The study was conducted to determine whether corosolic acid could protect the myocardium of diabetic rats from damage caused by isoproterenol (ISO) and, if so, how peroxisome proliferator-activated receptor gamma (PPAR-γ) activation might contribute into this protection. Diabetes in the rats was induced by streptozotocin (STZ), and it was divided into four groups: the diabetic control group, diabetic rats treated with corosolic acid, diabetic rats treated with GW9662, and diabetic rats treated with corosolic acid plus GW9662. The study was carried out for 28 days. The diabetic control and ISO control groups showed a decrease in mean arterial pressure (MAP) and diastolic arterial pressure (DAP) and an increase in systolic arterial pressure (SAP). The rat myocardium was activated by corosolic acid treatment, which elevated PPAR-γ expression. A histopathological analysis showed a significant reduction in myocardial damage by reducing myonecrosis and edema. It was found that myocardial levels of CK-MB and LDH levels were significantly increased after treatment with corosolic acid. By decreasing lipid peroxidation and increasing endogenous antioxidant levels, corosolic acid therapy showed a significant improvement over the ISO diabetic group. In conclusion, our results prove that corosolic acid can ameliorate ISO-induced acute myocardial injury in rats. Based on these results, corosolic acid seems to be a viable new target for the treatment of cardiovascular diseases and other diseases of a similar nature.

Effects of Taraxerol on Oxidative and Inflammatory Mediators in Isoproterenol-Induced Cardiotoxicity in an Animal Model.

Myocardial infarction (MI) continues to be an important issue in healthcare systems worldwide, leading to high rates of morbidity and mortality. Despite ongoing efforts towards the development of preventive measures and treatments, addressing the challenges posed by MI remains difficult both in developed and developing countries. However, researchers recently investigated the potential cardioprotective effects of taraxerol utilizing an isoproterenol (ISO)-induced cardiotoxicity model among Sprague Dawley rats. Specifically, subcutaneous tissue injections consisting of 5.25 mg/kg or 8.5 mg/kg ISO were administered over two consecutive days as stimuli to induce cardiac injury. To investigate the possibility of preventing damage caused by ISO-induced cardiotoxicity by taraxerol treatment, five groups were formed: a normal control group (1% Tween 80), an ISO control group, an amlodipine group administered 5 mg/kg/day, and various doses of taraxerol. The study results showed that treatment significantly reduced cardiac marker enzymes. Additionally, pretreatment with taraxerol increased myocardial activity in SOD and GPx, leading to significant reductions in serum CK-MB levels along with MDA, TNF-α, and IL-6. Further histopathological analysis supported these observations, as treated animals had less cellular infiltration compared to untreated ones. These multifaceted findings suggest that oral administration of taraxerol could potentially protect hearts from ISO-caused damage by increasing endogenous antioxidant concentrations while decreasing pro-inflammatory cytokines.

Groundwater quality assessment using SPSS based on multivariate statistics and water quality index of Gaya, Bihar (India).

Groundwater is a valuable resource for developmental activities, and its demand is growing as surface water becoming scarce. Groundwater demand is increasing, resulting in reduction in water level and deterioration in water quality. A total of 156 groundwater samples were taken from Gaya, a district in Bihar (India), to check the safety of drinking water. The quality of groundwater was assessed using a water quality index (WQI). Analysed samples were assessed using a variety of physicochemical characteristics, and statistical methods principal component analysis (PCA) and cluster analysis (CA) were used as they are effective and efficient. As per the Gibbs, plot majority of the sample falls in the rock-water interaction and some evaporation dominance field. The domination of major cation in the order of Ca2+ > Mg2+ > Na+ and the major anions followed the order of HCO3- > [Formula: see text]>[Formula: see text]>[Formula: see text]>[Formula: see text]. The KMO's sample adequacy value of 0.703 and the significance level of Bartlett's test of sphericity (0.0001) were indicating that PCA may be implemented. Using the PCA, the three components recovered explained 69.58% of the total variation. Cluster analysis classified the groundwater sample into three cluster based on the similarities among chemical parameters involved in groundwater quality. HCA exhibit less, intermediate, and heavily mineralized groundwater characteristics of groups I, II, and III, respectively. The major parameters affecting the water quality in the study region are TDS, Ca2+, Mg2+, HCO3-, [Formula: see text]. WQI indicates 17% of the sample were found to be of very poor quality and not consumable. The study's findings offer insights and understanding into groundwater pollution regimes. These results used for water quality assessment leading to improved environmental management and planning and in decision-making for water quality management.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation.

Background: Novel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. Objective: Synthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. Method: Thiosemicarbazone derivatives (4-13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4-13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. Results: The synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

Synthesis, molecular structure and urease inhibitory activity of novel bis-Schiff bases of benzyl phenyl ketone: A combined theoretical and experimental approach.

Background: Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. Objective: Synthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. Method: In the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. Results: The prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3-9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.

Novel Bis-Schiff's base derivatives of 4-nitroacetophenone as potent α-glucosidase agents: Design, synthesis and in silico approach.

Bis-Schiff's base derivatives of 4-nitroacetophenone (1-18) were synthesized in good yields by reacting hydrazone of 4-nitroacetophenone with substituted aldehydes and ketones with catalytic amount of acetic acid. The structures of synthesized products (1-18) were deduced with the help of spectroscopic techniques like 1H NMR, 13C NMR and HR-ESIMS. The synthesized bis-Schiff's bases were assessed for their α-glucosidase inhibitory activity where compound 4 (IC50 = 2.79 ± 0.04 µM), 1 (IC50 = 9.76 ± 0.31 µM), 6 (IC50 = 11.37 ± 0.20 µM), 17 (IC50 = 14.10 ± 0.12 µM), 14 (IC50 = 17.21 ± 0.28 µM), and 8 (IC50 = 20.73 ± 0.53 µM), showed a very high potential for inhibition of α-glucosidase. Compounds 11, 15, 16, 2, 18, 7, and 5 showed significant inhibition against alpha-glucosidase with IC50 values 22.98 ± 0.34, 24.45 ± 0.53, 27.31 ± 0.29, 40.56 ± 0.60, 41.58 ± 0.47, 46.53 ± 0.76, and 47.46 ± 0.89 µM, respectively. Furthermore, compound 10 (IC50 = 52.63 ± 0.74 µM), 12 (IC50 = 70.80 ± 3.59 µM), 3 (IC50 = 82.68 ± 0.69 µM), 13 (IC50 = 88.89 ± 4.25 µM), and 9 (IC50 = 94.58 ± 0.86 µM) showed moderate activity towards the inhibition of α-glucosidase enzyme. All these compounds were compared with acarbose (IC50 = 875.75 ± 1.24 µM) as a standard α-glucosidase inhibitor. Molecular docking was used to know the molecular bases of such high activities against α-glucosidase. High docking scores were recorded implying significant interactions between the active compounds and amino acid residues of the active site of α-glucosidase.

Phytochemical Screening, In Vitro and In Silico Studies of Volatile Compounds from Petroselinum crispum (Mill) Leaves Grown in Saudi Arabia.

The herbal plant Petroselinum crispum (P. crispum) (Mill) is commonly available around the world. In this study, the leaves of the herbal plant P. crispum were collected from the central region of Al-Kharj, Saudi Arabia, to explore their in vitro pharmacological activity. Essential oil from the leaves of P. crispum was isolated using the hydrodistillation method. The composition of P. crispum essential oil (PCEO) was determined using Gas chromatography-mass spectrometry (GC-MS). A total of 67 components were identified, representing approximately 96.02% of the total volatile composition. Myristicin was identified as the principal constituent (41.45%). The in vitro biological activity was assessed to evaluate the antioxidant, antimicrobial, and anti-inflammatory potential of PCEO. PCEO showed the highest antimicrobial activity against Candida albicans and Staphylococcus aureus among all the evaluated microbial species. In vitro anti-inflammatory evaluation using albumin and trypsin assays showed the excellent anti-inflammatory potential of PCEO compared to the standard drugs. An in silico study of the primary PCEO compound was conducted using online tools such as PASS, Swiss ADME, and Molecular docking. In silico PASS prediction results supported our in vitro findings. Swiss ADME revealed the drug likeness and safety properties of the major metabolites present in PCEO. Molecular docking results were obtained by studying the interaction of Myristicin with an antifungal (PDB: 1IYL and 3LD6), antibacterial (PDB: 1AJ6 and 1JIJ), antioxidant (PDB: 3NM8 and 1HD2), and anti-inflammatory (3N8Y and 3LN1) receptors supported the in vitro results. Therefore, PCEO or Myristicin might be valuable for developing anti-inflammatory and antimicrobial drugs.

Rutin Improves Anxiety and Reserpine-Induced Depression in Rats.

Mental disorders have a poor clinical prognosis and account for approximately 8% of the global burden of disease. Some examples of mental disorders are anxiety and depression. Conventional antidepressants have limited efficacy in patients because their pharmacological effects wear off, and side effects increase with prolonged use. It is claimed that herbal medicine's antioxidant capacity helps regulate people's mood and provide a more substantial pharmacological effect. With this background, the purpose of this study is to investigate the effect of rutin on reserpine-induced anxiety and depression in rats. The animals were divided into groups of six rats each: normal control (water), a depression model, a rutin-treated rat model, and an amitriptyline-treated rat model. According to the results, 14 days of treatment with rutin, once daily, showed a modest antidepressant effect. This effect was mediated by increased serotonin, norepinephrine, and dopamine levels in cortical and hippocampal regions. The antioxidant and vasodilator properties of rutin may contribute to its antidepressant properties. According to this study, rutin has shown antidepressant effects by reducing antioxidant activity and acetylcholinesterase.

Design, Synthesis, Crystal Structure, In Vitro and In Silico Evaluation of New N'-Benzylidene-4-tert-butylbenzohydrazide Derivatives as Potent Urease Inhibitors.

BACKGROUND: Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N' benzylidene-4-(tert-butyl)benzohydrazide derivatives (4-26) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and 1H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC50 = 13.33 ± 0.58-251.74 ± 6.82 µM as compared with standard thiourea having IC50 = 21.14 ± 0.425 µM. Two compounds, 6 and 25, were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.