Identification of natural compounds (proanthocyanidin and rhapontin) as high-affinity inhibitors of SARS-CoV-2 Mpro and PLpro using computational strategies.

Introduction: The emergence of a new and highly pathogenic coronavirus (SARS-CoV-2) in Wuhan (China) and its spread worldwide has resulted in enormous social and economic losses. Amongst many proteins encoded by the SARS-CoV-2 genome, the main protease (Mpro) or chymotrypsin-like cysteine protease (3CLpro) and papain-like protease (PLpro) serve as attractive drug targets. Material and methods: We screened a library of 2267 natural compounds against Mpro and PLpro using high throughput virtual screening (HTVS). Fifty top-scoring compounds against each protein in HTVS were further evaluated by standard-precision (SP) docking. Compounds with SP docking energy of ≤ -8.0 kcal/mol against Mpro and ≤ -5.0 kcal/mol against PLpro were subjected to extra-precision (XP) docking. Finally, six compounds against each target proteins were identified and subjected to Prime/MM-GBSA free energy calculations. Compounds with the lowest Prime/MM-GBSA energy were subjected to molecular dynamics simulation to evaluate the stability of protein-ligand complexes. Results: Proanthocyanidin and rhapontin were identified as the most potent inhibitors of Mpro and PLpro, respectively. Analysis of protein-inhibitor interaction revealed that both protein-inhibitor complexes were stabilized by hydrogen bonding and hydrophobic interactions. Proanthocyanidin interacted with the catalytic residues (His41 and Cys145) of Mpro, while rhapontin contacted the active site residues (Trp106, His272, Asp286) of PLpro. The docking energies of proanthocyanidin and rhapontin towards their respective targets were -10.566 and -10.022 kcal/mol. Conclusions: This study's outcome may support application of proanthocyanidin and rhapontin as a scaffold to build more potent inhibitors with desirable drug-like properties. However, it requires further validation by in vitro and in vivo studies.

Combined application of zinc oxide and iron nanoparticles enhanced Red Sails lettuce growth and antioxidants enzymes activities while reducing the chromium uptake by plants grown in a Cr-contaminated soil.

Soil contamination with chromium (Cr) is becoming a primary ecological and health concern, specifically in the Kasur and Sialkot regions of Pakistan. The main objective of the current study was to evaluate the impact of foliar application of zinc oxide nanoparticles (ZnO NPs) (0, 25, 50, 100 mg L-1) and Fe NPs (0, 5, 10, 20 mg L-1) in red sails lettuce plants grown in Cr-contaminated soil. Our results showed that both ZnO and Fe NPs improved plant growth, and photosynthetic attributes by minimizing oxidative stress in lettuce plants through the stimulation of antioxidant enzyme activities. At ZnO NPs (100 mgL-1), dry weights of shoots and roots and fresh weights of shoots and roots were improved by 53%, 58%, 34%, and 45%, respectively, as compared to the respective control plants. The Fe NPs treatment (20 mgL-1) increased the dry weight of shoots and the roots and fresh weights of shoots and roots by 53%, 76%, 42%, and 70%, respectively. Application of both NPs reduced the oxidative stress caused by Cr, as evident by the findings of the current study, i.e., at the ZnO NPs (100 mgL-1) and Fe NPs (20 mgL-1), the EL declined by 32% and 44%, respectively, in comparison with respective control plants. Moreover, Fe and ZnO NPs enhanced the Fe and Zn contents in red sails lettuce plants. Application of ZnO NPs at 100 mg L-1 and Fe NPs at 20 mg L-1, improved the Zn and Fe contents in plant leaves by 86%, and 68%, respectively, as compared to the control plants. This showed that the exogenous application of these NPs helped in Zn and Fe fortification in plants. At similar of concenteration ZnO NPs, CAT and APX activities were improved by 52% and 53%, respectively. Similarly, the POD contents were improved by 17% and 45% at 5 and 10 mg/L of Fe NPs. Furthermore, ZnO and Fe NPs limited the Cr uptake by plants, and the concentration of Cr in the leaves of lettuce was under the threshold limit. The exogenous application of ZnO NPs (100 mg L-1) and Fe NPs (20 mg L-1) reduced the Cr uptake in the leaves of red sails lettuce by 57% and 51%, respectively. In conclusion, ZnO and Fe NPs could be used for the improvement of plant growth and biomass as well as nutrient fortification in stressed environments. These findings not only underscore the efficacy of nanoparticle-assisted phytoremediation but also highlight its broader implications for sustainable agriculture and environmental health. However, future studies on other crops with molecular-level investigations are recommended for the validation of the results.

ZnO and Fe NPs improved the growth and photosynthesis of red sails lettuce plantsBoth NPs enhanced antioxidants enzymes activities in stressed plantsNPs mediated response reduced the oxidative stress and Cr uptake in red sails lettuceZnO and Fe NPs resulted in Zn and Fe fortification, respectively, in red sails lettuce.

Domestic wastewater treatment by Pistia stratiotes in constructed wetland.

The objective of the study was to evaluate the performance of Pistia stratiotes for treatment of domestic wastewater in a free surface water flow constructed wetland. The objective of the study was to evaluate contaminants removal efficiency of the constructed wetland vegetated with P. stratiotes in treatment of domestic wastewater against Hydraulic retention time (HRT) of 10, 20 and 30 days was investigated. This asks for newer and efficient low-cost nature-based water treatment system which along with cost takes into consideration the sustainability of the ecosystem. Five constructed wetland setups improved the wastewater quality and purify it significantly by reducing the TDS by 83%, TSS by 82%, BOD by 82%, COD by 81%, Chloride by 80%, Sulfate by 77%, NH3 by 84% and Total Oil and Grease by 74%. There was an increase in pH of about 11.9%. Color and odor of wastewater was also improved significantly and effectively. It was observed that 30 days' HRT was optimum for the treatment of domestic wastewater. The final effluent was found to be suitable as per national environmental quality standards and recycled for watering plants and crop irrigation but not for drinking purposes. The treatment in constructed wetland system was found to be economical, as the cost of construction only was involved and operational and maintenance cost very minimal. Even this research was conducted on the sole purpose of commuting the efficiency of pollutant removal in short span time.

Exploring therapeutic potential of Rutin by investigating its cyclin-dependent kinase 6 inhibitory activity and binding affinity.

Cyclin-dependent kinase 6 (CDK6) participates in numerous signalling pathways and regulates various physiological processes. Due to its unique structural features and promising therapeutic potential, CDK6 has emerged as a drug target for designing and developing small-molecule inhibitors for anti-cancer therapeutics and other CDK6-associated diseases. The current study evaluates binding affinity and the inhibitory potential of rutin for CDK6 to develop a proof of concept for rutin as a potent CDK6 inhibitor. Molecular docking and 200 ns all-atom simulations reveal that rutin binds to the active site pocket of CDK6, forming interactions with key residues of the binding pocket. In addition, the CDK6-rutin complex remains stable throughout the simulation trajectory. A high binding constant (Ka = 7.6 × 105M-1) indicates that rutin has a strong affinity for CDK6. Isothermal titration calorimetry has further validated a strong binding of rutin with CDK6 and its spontaneous nature. The kinase activity of CDK6 is significantly inhibited by rutin with an IC50 value of 3.10 µM. Our findings highlight the significant role of rutin in developing potential therapeutic molecules to manage cancer and CDK6-associated diseases via therapeutic targeting of CDK6.

Harnessing memantine in Alzheimer's disease therapy through inhibition of microtubule affinity-regulating kinase: Mechanistic insights.

Alzheimer's disease (AD) is one of the neurodegenerative disorder that primarily affects memory, thinking, and behavior, eventually leading to severe cognitive impairment. Therapeutic management of AD is urgently needed to improve the quality and lifestyle of patients. Tau phosphorylating kinases are considered attractive therapeutic targets. Microtubule affinity-regulating kinase 4 (MARK4) is directly linked with pathological phosphorylations of tau, highlighting its role in the therapeutic targeting of AD. The current manuscript shows the MARK4 inhibitory effect of Memantine (MEM), a drug used in treating AD. We have performed fluorescence based binding measurements, enzyme inhibition assay, docking and molecular dynamics (MD) simulations to understand the binding of of MARK4 and MEM and subsequent inhibition in the kinase activity. A 100 ns MD simulations provided a detailed analysis of MARK4-MEM complex and the role of potential critical residues in the binding. Finally, this study provides molecular insights into the therapeutic implication of MEM in AD therapeutics. We propose MEM effectively inhibits MARK4, it may be implicated in the development of targeted and efficient treatments for AD.

Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development as PfCDPK1 kinase inhibitors.

The rapid emergence of resistance to existing frontline antimalarial drugs emphasizes a need for the development of target-oriented molecules with novel modes of action. Given the importance of a plant-like Calcium-Dependent Protein Kinase 1 (PfCDPK1) as a stand-alone multistage signalling regulator of P. falciparum, we designed and synthesized 7-chloroquinoline-indole-chalcones tethered with a triazole (CQTrICh-analogs 7 (a-s) and 9) directed towards PfCDPK1. This was accomplished by reacting substituted 1-phenyl-3-(1-(prop-2-yn-1-yl)-1H-indol-3-yl) prop-2-en-1-one and 1-(prop-2-yn-1-yl)-1H-indole-3-carbaldehyde with 4-azido-7-chloroquinoline, respectively via a 'click' reaction. The selected CQTrICh-analogs: 7l and 7r inhibited the growth of chloroquine-sensitive 3D7 strain and -resistant RKL-9 isolate of Plasmodium falciparum, with IC50 values of 2.4 µM & 1.8 µM (7l), and 3.5 µM & 2.7 µM (7r), respectively, and showed no apparent hemolytic activity and cytotoxicity in mammalian cells. Intra-erythrocytic progression studies revealed that the active hybrids: 7l and 7r are effective against the mature stages of the parasite. 7l and 7r were found to stably interact with the catalytically active ATP-binding pocket of PfCDPK1 via energetically favourable H-bonds. The interaction was confirmed in vitro by microscale thermophoresis and kinase assays, which demonstrated that the active hybrids interact with PfCDPK1 and inhibit its kinase activity which is presumably responsible for the parasite growth inhibition. Interestingly, 7l and 7r showed no inhibitory effect on the human kinases, indicating their selectivity for the parasite kinase. We report the antiplasmodial potential of novel kinase-targeting bio-conjugates, a step towards developing pan-kinase inhibitors which is a prerequisite for multistage anti-malarial protection.

A Comprehensive Multispectroscopic and Computational Analysis of the Interaction between Plant-Based Antiplasmodial Compounds and Bovine Serum Albumin.

This study was conducted to explore the interaction between two plant-based antiplasmodial compounds, gartanin and friedelin, and bovine serum albumin (BSA). The objectives aimed to elucidate the binding characteristics, structural changes, and thermodynamic parameters associated with the interaction. Various methods were used including UV-vis, fluorescence, and circular dichroism spectroscopy, supported by molecular docking and molecular dynamics simulation. The results showed a concentration-dependent interaction between the antiplasmodial compounds and BSA, revealing changes in protein conformation and stability. The obtained results showed that the plant products bound with BSA through static quenching with moderate binding affinity (104 M-1) with BSA. Thermodynamic parameters and structural transitions calculated from spectroscopic methods revealed that hydrogen bond and van der Waals forces caused the partial conformational alteration in the secondary structure of BSA as the α-helical content decreased with an increase in ß sheets, random coils, and other structures. Computational analysis provided insights into the binding sites and affinities. The study enhances our understanding of the molecular interactions between BSA protein and antiplamodial compounds obtained from plants, supporting the research of choosing, designing, and optimizing molecules for biomedical applications with a focus on selectively targeting their binding sites.

Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of -8.35, -9.67 and -8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski's rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

Potential of Capparis decidua plant and eggshell composite adsorbent for effective removal of anionic dyes from aqueous medium.

The presence of hazardous dyes in wastewater poses significant threats to both ecosystems and the natural environment. Conventional methods for treating dye-contaminated water have several limitations, including high costs and complex operational processes. This study investigated a sustainable bio-sorbent composite derived from the Capparis decidua plant and eggshells, and evaluated its effectiveness in removing anionic dyes namely tartrazine (E-102), methyl orange (MO), and their mixed system. The research examines the influence of initial concentration, contact time, pH, adsorbent dosage, and temperature on the adsorption properties of anionic dyes. Optimal removal of tartrazine (E-102), methyl orange (MO), and their mixed system was achieved at a pH of 3. The equilibrium was achieved at 80 min for MO and mixed systems, and 100 min for E-102. The adsorption process showed an exothermic nature, indicating reduced capacity with increasing temperature, consistent with heat release during adsorption. Positive entropy values indicated increased disorder at the solid-liquid interface, attributed to molecular rearrangements and interactions between dye molecules and the adsorbent. Isotherm analysis using Langmuir, Freundlich, Temkin, and Redlich-Peterson models revealed that the Langmuir model best fit the experimental data. The maximum adsorption capacities of 50.97 mg/g, 52.24 mg/g, and 56.23 mg/g were achieved for E-102, MO, and the mixed system under optimized conditions, respectively. The pseudo-second-order kinetic model demonstrated the best fit, indicating that adsorption occurs through physical and chemical interactions such as electrostatic attraction, pore filling, and hydrogen bonding. Hence, the developed bio-sorbent could be a sustainable and cost-effective solution for the treatment of anionic dyes from industrial effluents.

Investigating the role of thymol as a promising inhibitor of pyruvate dehydrogenase kinase 3 for targeted cancer therapy.

Protein kinases have emerged as major contributors to various diseases. They are currently exploited as a potential target in drug discovery because they play crucial roles in cell signaling, growth, and regulation. Their dysregulation is associated with inflammatory disorders, cancer, and neurodegenerative diseases. Pyruvate dehydrogenase kinase 3 (PDK3) has become an attractive drug target in cancer therapeutics. In the present study, we investigated the effective role of thymol in PDK3 inhibition due to the high affinity predicted through molecular docking studies. Hence, to better understand this inhibition mechanism, we carried out a 100 ns molecular dynamics (MD) simulation to analyse the dynamics and stability of the PDK3-thymol complex. The PDK3-thymol complex was stable and energetically favourable, with many intramolecular hydrogen bond interactions in the PDK3-thymol complex. Enzyme inhibition assay showed significant inhibition of PDK3 by thymol, revealing potential inhibitory action of thymol towards PDK3 (IC50 = 2.66 µM). In summary, we established thymol as one of the potential inhibitors of PDK3, proposing promising therapeutic implications for severe diseases associated with PDK3 dysregulation. This study further advances our understanding of thymol's therapeutic capabilities and potential role in cancer treatment.

Identification of High-Affinity Inhibitors of TANK-Binding Kinase 1 (TBK1): A Promising Frontier for Controlling Inflammatory Signaling in Cancer.

BACKGROUND: TANK-binding kinase 1 (TBK1) is an important serine/threonine kinase involved in inflammatory signaling pathways, influencing cellular processes such as proliferation, programmed cell death, autophagy, and immune response regulation. Dysregulation of TBK1 has been linked to cancer progression and neurodegenerative disorders, making it an attractive target for therapeutic development. This study aimed to identify potential TBK1 inhibitors using a structure-based virtual screening approach. METHODS: We conducted a comprehensive screening of the ZINC database to identify compounds with high binding affinity for TBK1, employing molecular docking as the primary selection criterion. The top candidates were then subjected to extensive 200 ns molecular dynamics (MD) simulations to assess the conformational dynamics of TBK1 and the stability of the protein-ligand complexes, with a focus on ZINC02095133 and ZINC02130647. RESULTS: The findings revealed that TBK1 forms stable complexes with ZINC02095133 and ZINC02130647, demonstrating consistent interactions throughout the MD simulations. This suggests that these compounds hold promise as potential lead molecules for future therapies targeting TBK1. CONCLUSIONS: This study identifies ZINC02095133 and ZINC02130647 as promising TBK1 inhibitors with therapeutic potential. However, further experimental validation and optimization are required to develop novel inhibitors for diseased conditions associated with TBK1 signaling. These findings pave the way for future investigations into the clinical utility of these compounds in combating TBK1-related pathologies.

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products.

This study addressed the simplest and most efficient HPLC (high-performance liquid chromatography) method for the estimation of 5-fluorouracil (5-FU) from rat blood plasma by implementing the Hansen solubility parameters (HSP), computation prediction program, and QbD (quality by design) tool. The mobile phase selection was based on the HSP predictions and experimental data. The Taguchi model identified seven variables (preoptimization) to screen two factors (mobile phase ratio as A and column temperature as B) at three levels as input parameters in "CCD (central composite design)" optimization (retention time as Y1 and peak area as Y2). The stability study (freeze-thaw cycle and short- and long-term stability) was conducted in the rat plasma. Results showed that HSPiP-based HSP values and computational model-based predictions were well simulated with the experimental solubility data. Acetonitrile (ACN) was relatively suitable over methanol as evidenced by the experimental solubility value, HSP predicted parameters (δh of 5-FU - δh of ACN = 8.3-8.3 = 0 as high interactive solvent whereas δh of 5-FU - δh of methanol = 8.3-21.7 = -13.4), and instrumental conditions. CCD-based dependent variables (Y1 and Y2) exhibited the best fit of the model as evidenced by a high value of combined desirability (0.978). The most robust method was adopted at A = 96:4 and B = 40 °C to get earlier Y1 and high Y2 as evidenced by high desirability (D) = 0.978 (quadratic model with p < 0.0023). The estimated values of LLOD and LLOQ were found to be 0.11 and 0.36 µg/mL, respectively with an accuracy range of 94.4-98.7%. Thus, the adopted method was the most robust, reliable, and reproducible methodology for pharmacokinetic parameters after the transdermal application of formulations in the rat.

Synthesis, anticancer activity, molecular docking and molecular dynamics studies of some pyrazole-chalcone hybrids.

Four new hybrid compounds (H1-H4) bearing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. Compounds were assayed for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines. Besides, toxicity against normal cells was determined using the human umbilical vein endothelial cells (HUVEC). In silico molecular docking, molecular dynamics (MD) simulation and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were carried out to predict the binding modes, protein stability, drug-likeness and toxicity of the reported compounds. The in vitro anticancer activity of the tested compounds revealed dose-dependent cell-specific cytotoxicity. In silico studies revealed that the compounds have a good binding affinity, possess appropriate drug-likeness properties and have low toxicity profiles.Communicated by Ramaswamy H. Sarma.

An integrated docking and molecular dynamics simulation approach to discover potential inhibitors of activin receptor-like kinase 1.

Activin receptor-like kinase 1 (ALK1) is a transmembrane receptor involved in crucial signaling pathways associated with angiogenesis and vascular development. Inhibition of ALK1 signaling has emerged as a promising therapeutic strategy for various angiogenesis-related diseases, including cancer and hereditary hemorrhagic telangiectasia. This study aimed to investigate the potential of phytoconstituents as inhibitors of ALK1 using a combined approach of virtual screening and molecular dynamics (MDs) simulations. Phytoconstituents from the IMPPAT 2.0 database underwent virtual screening to identify potential inhibitors of ALK1. The compounds were initially filtered based on physicochemical parameters, following Lipinski's rules and the PAINS filter. Subsequently, compounds demonstrating high binding affinities in docking analysis were further analyzed. Additional assessments, including ADMET, PAINS, and PASS evaluations, were conducted to identify more potent hits. Through interaction analysis, a phytoconstituent, Candidine, exhibited appreciable affinity and specific interactions with the ALK1 active site. To validate the results, MD simulations and principal components analysis were performed. The MD simulations demonstrated that Candidine stabilized the ALK1 structure and reduced conformational fluctuations. In conclusion, Candidine shows promising potential as binding partners of ALK1. These findings provide a foundation for further exploration and development of Candidine as a lead molecule for therapeutic interventions targeting ALK1-associated diseases.

Blood-stage antimalarial activity, favourable metabolic stability and in vivo toxicity of novel piperazine linked 7-chloroquinoline-triazole conjugates.

The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development.

Health risks assessment and source admeasurement of potentially dangerous heavy metals (Cu, Fe, and Ni) in rapidly growing urban settlement.

Environmental contamination is a global challenge that impacts every aspect of ecosystem. The contaminants from anthropogenic or industrial trash continually recirculate into the environment, agricultural land, plants, livestock, and ultimately into humans by way of the food chain. After an increase in human and farmland animal deaths from illnesses due to contaminated drinking water, toxic metal water poisoning has remained a global concern. Diverse environmental and enforcement organisations have attempted to regulate the activities that serve as precursors to these heavy metals which have been proven ineffective. These unnecessary metals have severely hampered most biological processes. The presence of hazardous metals, which are harmful at extremely high levels and have a negative effect on the health of living bodies generally degrades the nutritional value of water. In order to evaluate the heavy metals (Cu, Ni, and Fe) toxicity of groundwater in pri-urban areas, the current study was conducted that have been considered as advance solution to tackle climate change which influence coastal ecosystem. Additionally, the impacts of soil and plant (spinach and brassica) contamination from groundwater were evaluated. The heavy metals were examined in the soil and groundwater samples (Pb, Fe and Ni). While Fe concentrations in water samples were found to be high as 1.978 mg/L as compared to Ni and Cu values low. According to WHO guidelines, the mean value of Fe exceeds the limit value. Similarly, Cu had a higher mean value (0.7 mg/L) in soil samples than other metals (Ni and Fe). In comparison to Ni and Cu, the Fe concentrations in spinach and brassica plants samples are greater, at 17.2 mg/L and 3.22 mg/L, respectively. The possible effects of metal poisoning of groundwater and plants on human health have been assessed using the Hazard Quotient (HQ), Evaluated Daily Intake (EDI), and Incremental Life Time Cancer Risk formulas (ILTCR). When drinking Ni-contaminated water, humans are more at risk of developing cancer (0.0031) than Fe and Cu. Metal concentrations in water and brassica showed substantially more scattered behaviour on the plot and no meaningful relationship, although PCA and masked matrix correlation showed a fair association between Ni and Cu in brassica (r2: 0.46) and Fe and Ni in spinach (r2: 0.31). According to the study's findings, it is anticipated that special management and groundwater monitoring will be needed in the examined area to reduce the health risks related to drinking water that has been contaminated with metals.

Exploring solubility and energetics: Dissolution of biologically important l-threonine in diverse aqueous organic mixtures across the temperature range of 288.15 K to 308.15 K.

This research provides a thorough investigation into the solubility behavior and solution thermodynamics of l-threonine in significant organic solvent systems. The work was done on measuring the actual solubility and subsequently calculating overall transfer solvation free energetics (∆Genergetic0i) and transfer entropies (∆St0i) at a temperature of 298.15 K. These measurements were performed as l-threonine transitioned from water to different water-organic mixed solvents systems. The saturated solubilities of l-threonine were determined using the 'gravimetric method' at five equidistant temperatures namely 288.15 K, 293.15 K, 298.15 K, 303.15 K and 308.15 K. By analyzing the data on solubility, we further obtained the different energies involved in solvation related issues. In the case of single solvents, the nature of solubility of l-threonine was observed like: dimethylsulfoxide (DMSO) < acetonitrile (ACN) < N, N-dimethylformamide (DMF) < ethylene glycol (EG) < water (H2O), irrespective of the experimental conditions. Specifically, at 298.15 K, the solubilities of l-threonine in single solvents were found to be as follows: 0.8220 mol per kg of water, 0.3101 mol per kg of EG, 0.1337 mol per kg of DMF, 0.1107 mol per kg DMSO and 0.1188 mol per kg of ACN. This research critically examines the relationship between the experimental saturated solubility of l-threonine and the complex properties influencing its solvation energy in diverse aqueous organic solvent systems.

Probing Baicalin as potential inhibitor of Aurora kinase B: A step towards lung cancer therapy.

Cell cycle regulators play pivotal roles as their dysregulation, leads to atypical proliferation and intrinsic genomic instability in cancer cells. Abnormal expression and functioning of Aurora kinase B (AURKB) are associated with cancer pathogenesis and thus exploited as a potential therapeutic target for the development of anti-cancer therapeutics. To identify effective AURKB inhibitors, a series of polyphenols was investigated to check their potential to inhibit recombinant AURKB. Their binding affinities were experimentally validated through fluorescence binding studies. Enzyme inhibition assay revealed that Mangiferin and Baicalin significantly inhibited AURKB activity with an IC50 values of 20.0 µM and 31.1 µM, respectively. To get atomistic insights into the binding mechanism, molecular docking and MD simulations of 100 ns were performed. Both compounds formed many non-covalent interactions with the residues of the active site pocket of AURKB. In addition, minimal conformational changes in the structure and formation of stable AURKB-ligand complex were observed during MD simulation analysis. Finally, cell-based studies suggested that Baicalin exhibited in-vitro cytotoxicity and anti-proliferative effects on lung cancer cell lines. Conclusively, Baicalin may be considered a promising therapeutic molecule against AURKB, adding an additional novel lead to the anti-cancer repertoire.

Study of Amiloride Binding to Human Serum Albumin: Insights from Thermodynamic, Spectroscopic, and Molecular Docking Investigations.

This study was undertaken to investigate the interaction between the sodium channel blocker amiloride (AML) and human serum albumin (HSA). A combination of multi-spectroscopic techniques and computational methods were employed to identify the AML binding site on HSA and the forces responsible for the formation of the HSA-AML complex. Our findings revealed that AML specifically binds to Sudlow's site II, located in subdomain IIIA of HSA, and that the complex formed is stabilized using van der Waals hydrogen-bonding and hydrophobic interactions. FRET analysis showed that the distance between AML and Trp214 was optimal for efficient quenching. UV-Vis spectroscopy and circular dichroism indicated minor changes in the structure of HSA after AML binding, and molecular dynamics simulations (MDS) conducted over 100 ns provided additional evidence of stable HSA-AML-complex formation. This study enhances understanding of the interaction between AML and HSA and the mechanism responsible.