Biochemistry
Anticancer Drug Development, Pharmaceutical Progress
Anticancer drug development is becoming complex and demanding because human cancer leads to 12% of global human mortality. Chemical and pharmacological breakthroughs play leading roles in updating drug evaluation and development for different types of tumors.
Chemical and pharmacological breakthroughs manifest in different facets. A large proportion of financial and workload increases in drug discovery must be paid off. In front of complexity difficulties and financial increase of drug development evaluative promotion must go miniature-wise and single-cell-wise. Multi-omics knowledge and technology are greatly expanded and understood in depth. This type of technical trend is suitable for current experimental exploration and clinical occasions. Technical and pharmacologic advances are especially emphasized to address this trend.
Presently the anticancer pharmaceutical study is multi-faceted and risk-taking. To keep up this momentum multi-disciplinary drug evaluation clinical selection and combination principles should be discovered. Past and futuristic chemical and pharmacological interactions and breakthroughs are discussed.
In summary the landscape of pharmaceutical investigation should be integrated with chemical and pharmacological knowledge in every facet of drug development and clinical personalization.
Use of Essential Oils for the Treatment of Fusarium oxysporum f. sp. Albedinis: Chemical Profile, In Vitro Antifungal Activity, and In Silico Investigation by Molecular Docking Study
Fusarium oxysporum f. sp. Albedinis a telluric fungal pathogen commonly found in soils is the causal agent of fungal vascular wilt of date palms in Moroccan oases. The infection by the pathogen leads to the death of the date palm after six months to two years which causes enormous economic and environmental damage.
The framework of this paper is to determine the chemical composition of six essential oils using GC-MS and their antifungal activity on the mycelial growth of Fusarium oxysporum f. sp. Albedinis as well as the molecular docking study to evaluate the inhibitory potential of fungal trypsin.
The essential oils were extracted from different parts of the plants (whole plant flowers and leaves) by steam distillation and were identified using gas chromatography-mass spectrometry (GC/MS). The antifungal assay of the extracted essential oils and their main components was assessed using the direct contact method with the fungus at different concentrations; the obtained results were evaluated by calculating the minimum inhibitory concentration (MIC) of each essential oil followed by an in-silico study of the major identified compounds for better understanding of the inhibitory potential against fungal trypsin activity.
The identification of the different bioactive compounds using GC-MS revealed that Rosmarinus officinalis Eo was characterized by eucalyptol 46.26% camphor 10.03% and β-pinene 6.63%; while Lavandula officinalis Eo was endowed by the presence of linalool 14.93% camphor 14.11% and linalyl acetate 11.17%. Furthermore Artemisia herba alba was rich in 135-cycloheptatriene 16-dimethyl- 36.44% camphor 22.50% and α-thujone 7.21%. While Eucalyptus globulus was rich in eucalyptol 74.32% β-Cymene 11.41% α-Pinene 6.96%. Finally Mentha pepirita and Mentha pulegium were both characterized by the presence of D-limonene 20.15% trans-carveol 19.59% D-Carvone 14.96% and pulegone (42.40%) 3-cyclopentene-1-ethanol 224-trimethyl- (11.28%) 134-trimethyl-3-cyclohexenyl-1-carboxaldehyde (9.68%) respectively. Regarding the in vitro all Eos from different plants exhibited pronounced antifungal effect. The MIC values recorded for E. globulus were MIC= 1.75 mg/L M. pulegium and L. officinalis (MIC= 1.80 mg/L) and M. piperita (MIC= 1.90 mg/L). The strongest inhibition potential was associated with R. officinalis EO (MIC= 1.15 mg/L) and A. herba alba EO (MIC= 1.60 mg/L). As for the computational study performed camphor one of the bioactive compounds showed its ability to act against trypsin which could be considered a potential candidate against Fusarium oxysporum f. sp. Albedinis.
The studied essential oils from different medicinal and aromatic plants showed significant antifungal activity probably due to the Camphor which could have an inhibitory effect on the Fusarium oxysporum f. sp. Albedinis trypsin. Further research should be conducted in vivo for a better understanding of the mechanism of action of these essential oils.
Hemi Synthesis, Anti-inflammatory and In-silico Alpha-amylase Inhibition of Novel Carlina Oxide Analogs
Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area.
This work aimed to synthesize some new analogs of carlina oxide by functionalizing the fifth position of the furan by different acyls groups using the Friedel-Crafts acylation approach and then assess the in-vitro anti-inflammatory activity and in-silico alpha-amylase inhibition effect of carlina oxide and its synthetic analogs.
The new analogs were synthesized at room temperature using different anhydrides with the presence of boron trifluoride diethyl etherate (BF3Et2O) as acid catalyst. A protein denaturation assay was performed to evaluate the anti-inflammatory activity while the molecular docking study was conducted using the Molecular Operating Environment (MOE) with three types of alpha-amylase sources: human salivary pancreatic alpha-amylase and Aspergillus oryzae alpha-amylase (PDB: 1Q4N 5EMY 7P4W respectively).
A total of four analogs of carlina oxide were obtained in yields of 60-7% and then identified with 1H and 13C NMR analysis. Additionally analog 1 exhibited the better anti-inflammatory effect with IC50 of 0.280 mg/mL. However the in-silico study showed that all the synthetic analogs have different interactions with human salivary alpha-amylase (1Q4N) and other interactions with 5EMY and 7P4W.
The new analogs of carlina oxide can have the potential to serve as an alternative agent for alpha-amylase inhibition contributing to the reduction of postprandial hyperglycemia.
Molecular Docking and In Silico ADME(T) Evaluation of Selective Phytochemical Inhibitors of VEGF2 Target for the Treatment of Diabetic Retinopathy
Diabetic retinopathy (DR) is the leading cause of vision loss in diabetic patients. Currently the treatment involves the use of glucocorticoids or a VEGF antagonist which are “off-label” at present. However the conventional method of drug discovery and development is a time-consuming process that requires more than a decade of meticulous research and huge financial support. While there are a few effective small organic molecules against DR that were identified many years ago nutraceuticals - naturally available functional foods containing vitamins antioxidants minerals fatty acids and amino acids - can also help delay the progression of some diseases.
In this study 43 phytochemical constituents from four medicinal plants were tested for their binding affinity to the influential VEGFR2 target of diabetic retinopathy. The study used a computational approach insilico molecular docking study structure-based drug design approach MSD (Molecular Dynamic Simulation analysis) insilico ADME (T) studies.
The study reported that all phytochemical constituents displayed good to the highest binding affinity than the standard ruboxistaurin. Six phytochemical constituents namely terchebulin pedunculagin punicalagin punicalin casuariniane and chebulagic acid exhibited equipotent to higher activity than the standard. These constituents displayed conventional hydrogen bonds pi-alkyl and pi-cation interactions to achieve their high binding affinity. The highest binding scores were chosen for analysis using MSD ensuring stability of the ligand-protein complex. Pharmacodynamic and pharmacokinetic properties were evaluated and their safety profile was validated.
This in silico screening study suggests that active phytomolecules present in medicinal plants may inhibit the VEGFR2 target. The best-docked compounds possessing drug-like properties can be used to develop potential inhibitors against DR or to mitigate its severity.
Synthesis, Docking Analysis, and Assessment of Chalcones for Antibacterial and Anthelmintic Activities
Chalcones have been demonstrated to contain numerous therapeutic qualities in recent years such as antibacterial antiviral anti-ulcerative antioxidant anti-inflammatory antihyperglycemic antimalarial antitubercular analgesic antiplatelet and anticancer activities.
To explorethe synthesis docking and characteristics of chalcones as antibacterial and anthelmintic compounds.
The chalcone derivatives (3a-3k) and (6l-6v) were synthesized via two selective different reactions based on the Claisen-Schmidt reaction. All synthesized compounds were evaluated for their antibacterial activity using an in vitro cup-plate method and their anthelmintic activity was assessed using an in vitro earthworm paralysis and death assay. To validate these findings conducted molecular docking experiments between the dihydrofolate reductase receptor (PDB ID: 4LAE) and the synthesised compounds (3a-3k) and (6l-6v) to determine catalytic interactions.
Compound 6(n) exhibited the greatest efficacy in biological in vitro activity against S. aureus compared to all other compounds examined. Compound 6(o) exhibited substantial efficacy against P. posthuma and E. coli. Emphasizing these findings the compounds 3(a) 3(g) 3(i) 6(n) and 6(o) demonstrated hydrogen bond interactions with certain amino acid residues of the receptor including THR 122 ASN 18 ASN19 GLN 96 SER 50 and ALA 8 during molecular docking.
The study results showed that the synthesised derivative (E)-1-(napthalen-2-yl)-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-one 6(n) had beneficial antibacterial properties against S. aureus while derivative (E)-1-(Napthalen-2-yl)-3-(4-trifluoromethyl)phenyl)prop-2-en-1-one 6(o) exhibited antibacterial activity against E. coli and anthlelmintic activity against P. posthuma.
Clove Aqueous Extract Alleviates Acute Kidney Injury Induced by Folic Acid in Rats
Acute Kidney Injury (AKI) is a common clinical disease that has a high incidence and mortality rate. Clove a robust natural source of bioactive chemicals and rich in secondary metabolites plays a wide range of biological roles.
The present study aimed to assess the ameliorative efficacy of clove extract against acute renal damage induced by folic acid in rats.
Gas Chromatography/Mass Spectrometry (GC/MS) was used to investigate the main components of clove extract. Folic acid at a dose of 250 mg/kg was delivered intraperitoneally to rats to induce AKI. Eighteen rats were divided into three groups: control AKI and AKI + clove extract (500 mg/kg).
The administration of clove extract significantly restored the levels of creatine urea uric acid sodium potassium chloride creatinine clearance and microalbumin to nearly normal levels. Also clove water extract inhibited oxidative stress by decreasing concentrations of Malondialdehyde (MDA) and Nitric Oxide (NO). Furthermore clove extract elevated the levels of Glutathione-reduced (GSH) Catalase (CAT) and Glutathione S-transferase (GST). Kidney section histology showed notable improvements after the administration of clove extract.
The clove water extract has been found to contain many bioactive components possessing antioxidant and anti-inflammatory properties effectively protecting against acute renal injury.
Ginsenosides as Promising Therapeutic Agents for Glioma: Mechanisms of Action and Future Perspectives
Brain cancers particularly gliomas are a significant cause of mortality worldwide. Gliomas are primary tumors of the central nervous system (CNS) and are characterized by diverse clinical and biological features. Despite advancements in clinical approaches and surgical techniques the treatment of high-grade gliomas still poses multiple challenges. This article focuses on a key active substance found in Panax ginseng called Ginsenosides. Ginsenosides belong to a specific class of triterpenoid saponins and have demonstrated various therapeutic effects including neuroprotective anticancer anti-inflammatory and neuroprotective functions. These compounds have shown potential in the treatment of gliomas and other cancers. Several pathways associated with ginsenosides such as Rg3 Rh2 Rd and Rb1 have been extensively studied and these compounds have been proposed as potential targets in glioma treatment. The precise mechanisms of action of ginsenosides in gliomas are still being investigated but their ability to modulate various signalling pathways and exert multiple therapeutic effects makes them promising candidates for further research and development. Clinical trials and additional studies are necessary to validate their therapeutic benefits and determine the optimal dosage administration route and potential combination with other treatment modalities. In summary ginsenosides the active compounds found in Panax ginseng exhibit various therapeutic effects including potential anti-cancer properties in gliomas. Their ability to modulate multiple pathways makes them promising targets for further research in the field of glioma treatment. However more studies are required to establish their effectiveness and safety in clinical settings.
An In-Silico Approach to Study the Effect of Phosphorylation (Ps129) on the Conformational Dynamics of Membrane Bound Α-Synuclein
Phosphorylated α-Synuclein (α-Syn) is present in relatively small levels in normal human brains but nearly all of the α-Syn in the Lewy bodies (LBs) that collect in the nigrostriatal region in the brain of Parkinsons disease patients is phosphorylated on serine 129 (pS129). Earlier studies suggested that mimicking phosphorylation at S129 may have an inhibitory effect on α-Syn aggregation and thus control α-Syn neuropathology. Although phosphorylation at S129 is associated with α-Syn inclusion in synucleinopathies the mechanisms by which this post-translational modification (PTM) influences aggregation and contributes to LB illness in the brain are yet to be understood.
This research aims to study the effect of phosphorylation (pS129) on the conformational dynamics of membrane-bound α-Syn using Molecular Dynamics (MD) simulations.
Using MD simulations this computational study has demonstrated the effect of PTM on the conformational dynamics of pS129 α-Syn and its lipid membrane association. To better understand the impact of pS129 on the aggregation of the α-Syn structure monomer with recent atomic details we have examined the MD trajectories conducted a salt-bridge interaction study Principal Component Analysis (PCA) and intra and inter-molecular hydrogen bond analysis.
The conformational structure of pS129 α-Syn was observed from the MD trajectory analysis to be stable throughout the simulation with higher compactness and reduced flexibility. The stability of the structure of pS129 α-Syn was also evaluated by 2-D and 3-D principal component analysis followed by a free energy landscape plot showing the global minima. The conformational snapshots and Ramachandran plot showed the absence of α-strands in the α-Syns Non-Amyloid Component Region (NAC) (71–82) which is necessary for aggregate formation.
Further the intermolecular hydrogen bonds analysis indicates that the NAC region is not embedded into the lipid bilayer and has limited association with the other regions of the protein. Our findings reveal salient features of pS129 modifications that inhibit α-Syn aggregation.
Intestinal Anti-Inflammatory and Antioxidant Potential of Arthrospira platensis Aqueous Extract on DNBS-Induced Colitis in BALB/c Mice
The most common Inflammatory Bowel Diseases (IBD) affecting the gastrointestinal system are Crohn's disease and ulcerative colitis. However the usual therapies for them are associated with a multitude of side effects. The blue-green microalgae Arthrospira platensis is known for its safety profile nutritional and medicinal properties in the treatment of different inflammatory and gastrointestinal disorders.
The objective of this study was to investigate the potential intestinal anti-inflammatory effects of the aqueous extract derived from Arthrospira platensis (AAP) in a mouse model of DNBS-induced colitis.
GC-MS and FTIR-ATR were used to determine the different types of chemical compounds found in the AAP extract. BALB/c mice that received DNBS intrarectally were treated with three doses (50 100 and 200 mg/kg) of AAP for three days. The inflammatory status was assessed daily using a Disease Activity Index (DAI). Mice were sacrificed on the third day and the extent of colonic damage was evaluated through both macroscopic and histological examinations. Finally biochemical assays of different markers (MDA NO and GSH) were performed.
The GC-MS analysis revealed the presence of eleven bioactive compounds including 2-thiophenecarboxylic acid 2-biphenyl ester palmitic acid 2-linoleoyl glycerol ethyl isoallocholate and methyl palmitate. In addition FTIR spectroscopy revealed the presence of amino hydroxyl and glucosidic groups. The treatment of colitic mice with AAP decreased the severity of colitis as demonstrated by the improvement in the clinical score and the reduction of colonic tissue damage as well as the modulation of the local biochemical marker levels.
The AAP effectively improves DNBS-induced colitis but its short treatment duration and focus on acute colitis highlight the need for further research on long-term and chronic effects.
Evaluation of Anti-Proliferative and Apoptosis-Inducing Activities of the New Ciprofloxacin Derivative on Human Leukemia NB4 Cells
Leukemic stem cells are considered to be the main cause of treatment failure and disease recurrence due to their resistance to most common therapies. Apoptosis induction is one of the highly effective methods for treating cancer. Ciprofloxacin is among the compounds whose antitumor effects have been confirmed.
In this study we investigated the anti-proliferative effect and induction of apoptosis by one of the derivatives of this family called 1-Cyclopropyl-6-fluoro-7-[4-(2-{[(1R2S5R)- 2-isopropyl-5-methylcyclohexyl]oxy}-2-oxoethyl)-piperazin-1-yl]-4-oxo-14-dihydroquinoline-3-carboxylic acid (ICH-CP) on NB4 cell line as an in vitro model of Acute promyelocytic leukemia (APL). NB4 cells were treated using the ICH-CP combination in various concentrations.
The viability of NB4 cells was evaluated by MTT assay and their morphology of apoptosis was examined by fluorescence microscopy. Flow cytometry and Annexin V/PI staining were used to quantify apoptosis. Finally the expression of three genes Bax Bcl-2 and Survivin was inquired by real-time PCR.
According to the results ICH-CP was able to destroy about 60% of NB4 cells in a dose and time-dependent manner. Light microscopy and fluorescence microscopy studies on treated cells confirmed the induction of apoptosis. Also the real-time PCR analysis showed that ICH-CP induces apoptosis in the NB4 cell line via the down-regulation of Survivin and Bcl-2 in contrast to the up-regulation of the Bax gene.
Based on the present data it seems that the novel compound can be a good candidate for the treatment of acute myeloid leukemia. Furthermore it is recommended to evaluate the qualification of ICH-CP as an adjunctive agent for other cancer cell lines.
Biogenic Silver Nanoparticles (AgNPs) Ameliorates Oxidative Biomarkers in Type-2 Diabetic Rats: In vitro and In vivo Report
Nanoparticles (NPs) are reliable biological tools for curative purposes through their application in nanomedicine. The present study synthesized and characterized silver nanoparticles (AgNPs) from Tetrapetra tetrapleura fruit. The investigation aims to examine the antidiabetic effect of the AgNPs using in vitro and in vivo models.
Briefly the synthesized AgNPs were confirmed by the application of ultraviolet-visible (UV-Vis) spectroscopy and five other techniques viz; transmission electron microscopy (TEM) techniques Fourier transform infrared (FTIR) spectroscopy energy dispersive X-ray spectroscopy (EDX) X-ray diffraction analysis (XRD) and scanning electron microscope (SEM). The in vitro model assay investigated the scavenging effect of AgNPS on 22-diphenyl-1-picrylhydrazyl (DPPH) superoxide anion (O2ˉ) hydroxyl anion (-OH) ferric reducing antioxidant power (FRAP) and α-amylase/α-glucosidase inhibitory activity. The in vivo model involving rats-induced type-2 diabetes with streptozotocin (STZ) was divided into six (6) groups of seven (7) rats each to assess antioxidative parameters.
The AgNPs scavenged free radicals (DPPH) and moderately inhibited (O2ˉ) hydroxyl anion (-OH) reduced ferric to ferrous ions and inhibited both α-amylase and α-glucosidase activity with increasing concentrations. Similarly AgNPs ameliorated oxidative stress imposed by type 2 diabetes on the rats’ tissues significantly (p < 0.05) depleting total cholesterol low-density lipoprotein (LDL) and increased total protein composite and high-density lipoprotein (HDL) contents. The AgNPs enhanced catalase and superoxide dismutase reduced glutathione (GSH) and concomitantly decreased malondialdehyde (MDA) levels in the tissue homogenate.
These findings provide scientific evidence for the first time finding the application of a biogenic compound synthesized from T. tetrapleura fruit in the treatment of type 2 diabetes.
In-vitro and In-silico α-amylase Inhibition Activity of Carlina Oxide and Aplotaxene Isolated From the Roots of Carthamus caeruleus and Rhaponticum acaule
Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area.
This work aimed to assess the in-vitro and in-silico α-amylase inhibition activities of carlina oxide and aplotaxene isolated from the roots of Carthamus caeruleus and Rhaponticum acaule respectively.
The essential oil from C. caeruleus roots was obtained using a Clevenger-type apparatus and the hexanoic extract from the roots of R. acaule was obtained through maceration. Major components of each plant were separated via column chromatography. The in-vitro α-amylase inhibition activity was evaluated using porcine pancreatic α-amylase while the molecular docking study was conducted using the Molecular Operating Environment (MOE) with three types of α-amylase: human salivary pancreatic α-amylase and Aspergillus oryzae α-amylase (PDB: 1Q4N 5EMY 7P4W respectively).
The in-vitro α-amylase inhibition results for the essential oil the hexanoic extract carlina oxide and aplotaxene showed that carlina oxide exhibited significant activity with IC50 of 0.42 mg/mL. However the in-silico study showed no interaction between aplotaxene and the three α-amylase enzymes whereas carlina oxide demonstrated one pi-cation interaction with 5EMY with the amino acid TYR 62 at a distance of 4.70 Å and two pi-H interactions with 7P4W with the amino acid LYS 383 at distances of 4.31 and 4 .03 Å.
In conclusion carlina oxide has the potential to serve as an alternative agent for α-amylase inhibition contributing to the reduction of postprandial hyperglycemia.
Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide
The brain is highly susceptible to oxidative damage due to excessive oxygen tension a high concentration of oxidizable substrates and low antioxidant capacity. Consequently oxidative stress is linked to several brain disorders and neurodegeneration. Sodium azide is a cytochrome oxidase inhibitor that promotes neurodegeneration by enhancing the release of excitotoxins and inducing oxidative stress through the peroxidation of membrane lipids. This process results in the release of intra-mitochondrial Ca+2 and H2O2 (ROS Dependent-Ca+2 release). Agmatine a biogenic amine is also referred to as a free radical scavenger protecting the brain from membrane collapse apoptosis and mitochondrial swelling.
This study was designed to identify the antioxidative effects of agmatine on sodium azide-induced oxidative stress in brain tissues.
Twenty-four male albino Wistar rats were allocated into two groups: a control group receiving water and a test group administered sodium azide (5 mg/kg intraperitoneally) for a duration of 14 days. Subsequently the animals were further subdivided and treated for an additional two weeks with either water or agmatine (100 mg/kg). Behavioral assessments were performed one-hour post-agmatine administration and brain homogenates were prepared for biochemical analyses.
The agmatine-treated group exhibited a significant increase (P<0.01) in both the number of entries and the time spent in the light box and the open arms of the light/dark transition box and elevated plus maze tests respectively. Additionally agmatine administration significantly enhanced (P<0.01) the total number of squares crossed in the open field test. Biochemical assessments revealed that agmatine treatment significantly reduced (P<0.01) the levels of reactive oxygen species and malondialdehyde. Moreover it significantly increased (P<0.01) the levels of antioxidant enzymes (superoxide dismutase catalase and glutathione peroxidase) and glutathione compared to the control group.
The present study revealed that agmatine has substantial effects on oxidative and antioxidant enzyme levels in sodium azide-induced oxidative stress. Agmatine-treated rats exhibited decreased reactive oxygen species levels and improvements in behavioral impairments resulting from sodium azide administration.
Protective Role of Ovothiol-A against Muscle and Kidney Injuries in Obese Rats
Obesity is a serious chronic metabolic disease impairing health damaging many organs such as kidneys and muscles. Ovothiol-A (Ovo-A) has been found to keep the redox balance normal in sea urchins indicating its antioxidant characteristics.
This study aims to investigate the protective effects of Ovo-A on kidneys and muscles in obese rats.
In-silco studies were performed on lactate dehydrogenase (LDH) and creatine kinase (CK) with Ovo-A to compute their binding affinities. Obesity was induced by high-fat diet (HFD) for 4 weeks. Wistar rats were used in this study as 6 rats per group as control HFD Ovo-A (200 and 400 mg/Kg p.o) groups.
Docking results have revealed that Ovo-A has affinities to bind to LDH (-8.5 kcal/mol) and CK (-17.7 kcal/mol). Ovo-A reduced the levels of uric acid urea creatinine LDH CK malondialdehyde (MDA) and nitric oxide (NO) while increasing the levels of glutathione (GSH) catalase (CAT) and glutathione-S-transferase (GST). Histopathological investigations have revealed that Ovo-A restored the renal and muscular structure.
The current study showed that Ovo-A has a protective effect on kidneys and muscles in obese rats. Ovo-A enhances renal and muscular functions by inhibiting LDH and CK activities and improving the antioxidant system. Ovo-A is more effective in the high dose.
Micro-Milli Scale for the Removal of Iron and Copper by a Positively Charged Foam before Nickel Colorimetric Detection using Handy Spectrometer
A simple alternative removal of iron and copper before the determination of nickel was proposed. The procedure was based on sampling a milligram sample and a micro-milliliter operation.
The method has been applied to jewelry items. A 50 mg sample was digested by 5 mL of nitric acid with heating. The obtained solution was added to KSCN before passing through polyurethane foam (PUF) (1 cm i.d. × 8 cm length). Some metal ions-SCN complexes (e.g. Fe(III) and Cu(II)) were retained in the column while Ni(II) ions were kept in the eluate. A 200-500 µL aliquot was added with 4-(2-pyridylazo)-resorcinol (PAR) as the color reagent. At least 30 µL of a portion was measured for the absorbance of the color product using a handy spectrometer.
The positively charged foam could remove iron and copper altogether before determining nickel. A standard calibration was a plot of absorbance versus Ni(II) concentration for 1-30 mg/L: Absorbance = 0.0123 [Ni(II) mg/L] + 0.0435 (R2=0.9945) with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.24 mg/L and 0.81 mg/L respectively. Two bracelet samples showed the presence of nickel at 0.97 ± 0.25 and 0.27 ± 0.04 mg/g respectively and agreed with the reference FlameAAS method.
The proposed method could be used to assay nickel in samples containing high levels of iron and copper such as jewelry. This will benefit general wearers with health concerns associated with nickel particularly in case of inexpensive accessories. The handy spectrometer used in the study might make be helpful to carry out these studies with a limited tight budget.
Emerging Role of Ionic Liquids in the Fabric Industry
Profitable interest in the pervasive packaging of ionic liquids has continued to increase due to its several advantages and environmentally pleasant nature. Fabric enterprise is stated to be the most important enterprise as a result of a rapid increase in the populace across the globe. Certain ionic beverages can dissolve textile fibers. Therefore ionic liquids are doubtlessly appropriate for material production and recycling. The dyeing of fabric substances involves numerous financial and ecological risks resulting in an excessive intake of water power and chemicals. Ionic liquids surpass through their extraordinarily low vapor pressure which enables them to deal with commonly used natural solvents. Moreover ionic liquids display excessive temperature-associated dielectric constants consequently displaying top-notch solvent strength for distinct fabric-associated substances inclusive of silicones keratin and cellulose. This article provides a brief review of the pertinent literature that focuses on historical patterns and practical commercial applications of ionic liquids before moving on to current developments in ionic liquids and the fabric industry.
Sustainable Green Synthesis and Molecular Docking Study of a Bis-Fused System Incorporating Pyrido[2,3-d]pyrimidine using Nanocatalyst under Microwave Condition
This study aimed to employ sustainable green methods in the synthesis of bis-fused cycles incorporating pyrido[23-d]pyrimidine moiety using a green catalyst nano ZnO catalyst by one-pot multicomponent reaction among 22'-(propane-13-diylbis(sulfanediyl)) bis(6-aminopyrimidin-4(3H)-one) 3 1H-indene-13(2H)-dione 4 and aromatic aldehydes 5.
The reactions proceeded with both conventional and microwave (MW) irradiation methods.
The microwave-assisted method carried out the reaction in 10 min and had high yields (89-95%).
A molecular docking simulation study was conducted using human serum albumin (PDB: ID (2XVQ)). The study revealed that compounds strongly fit into the active sites of the target protein.
Predicted Role of Acetyl-CoA Synthetase and HAT p300 in Extracellular Lactate Mediated Lactylation in the Tumor: In vitro and In silico Models
Background: As per the Warburg effect cancer cells are known to convert pyruvate into lactate. The accumulation of lactate is associated with metabolic and epigenetic reprogramming which has newly been suggested to involve lactylation. However the role of secreted lactate in modulating the tumor microenvironment through lactylation remains unclear. Specifically there are gaps in our understanding of the enzyme responsible for converting lactate to lactyl-CoA and the nature of the enzyme that performs lactylation by utilizing lactyl-CoA as a substrate. It is worth noting that there are limited papers focused on metabolite profiling that detect lactate and lactyl-CoA levels intracellularly and extracellularly in the context of cancer cells. Methods: Here we have employed an in-house developed vertical tube gel electrophoresis (VTGE) and LC-HRMS assisted profiling of extracellular metabolites of breast cancer cells treated by anticancer compositions of cow urine DMSO fraction (CUDF) that was reported previously. Furthermore we used molecular docking and molecular dynamics (MD) simulations to determine the potential enzyme that can convert lactate to lactyl-CoA. Next the histone acetyltransferase p300 (HAT p300) enzyme (PDB ID: 6GYR) was evaluated as a potential enzyme that can bind to lactyl- CoA during the lactylation process. Results: We collected evidence on the secretion of lactate in the extracellular conditioned medium of breast cancer cells treated by anticancer compositions. MD simulations data projected that acetyl- CoA synthetase could be a potential enzyme that may convert lactate into lactyl-CoA similar to a known substrate acetate. Furthermore a specific and efficient binding (docking energy -9.6 kcal/mol) of lactyl-CoA with p300 HAT suggested that lactyl-CoA may serve as a substrate for lactylation similar to acetylation that uses acetyl-CoA as a substrate. Conclusion: In conclusion our data provide a hint on the missing link for the lactylation process due to lactate in terms of a potential enzyme that can convert lactate into lactyl-CoA. This study helped us to project the HAT p300 enzyme that may use lactyl-CoA as a substrate in the lactylation process of the tumor microenvironment.
Tubulin-gene Mutation in Drug Resistance in Helminth Parasite: Docking and Molecular Dynamics Simulation Study
Background: Drug resistance is an important phenomenon in helminth parasites. Microtubules are among the key chemotherapeutic targets mutations of which lead to drug resistance. Objectives: The present study investigated the role of F167Y E198A and F200Y mutations in β- tubulin protein and their effect on albendazole binding. Methods: Brugia malayi β-tubulin protein models were generated using the SwissModel platform by submitting amino acid sequences. Mutations were carried out at amino acid sequences by changing F167Y E198A and F200Y. All the model proteins (one wild and three mutated) were docked with the anthelmintic drug albendazole using AutoDock vina-1.1.5. Docking complexes were further investigated for their binding stability by a Molecular Dynamic Simulation study using Gromacs-2023.2. The binding free energies of protein-ligand complexes were analyzed using the MM/PBSA package. Results: The docking study observed decreased ligand binding affinity in F167Y and E198A mutant proteins compared to wild proteins. MD simulation revealed the overall structural stability of the protein complexes during the simulation period. The simulation also observed more stable binding of albendazole in the active pocket of mutant proteins compared to wild-type proteins. Like ligand RMSD wild-type protein also showed higher amino acid residual flexibility. The flexibility indicates the less compactness of wild β-tubulin protein complexes compared to mutant proteinligand complexes. Van der Waals and electrostatic interactions were found to be the major energy in protein-ligand complexes. However due to higher solvation energy wild-type protein showed more flexibility compared to others. Conclusion: The study therefore concludes that mutations at positions 167 and 198 of the β- tubulin protein contribute to resistance to albendazole through weakened binding affinity. However the binding of albendazole binding to the proteins leads to structures becoming more stable and compact.
Synergistic Effect, and Therapeutic Potential of Aqueous Prickly Pear Extract. In vivo Neuroleptic, Catatonic, and Hypoglycemic Activity
Background: Prickly pear "Opuntia ficus indica (L.) Mill. "otherwise known as the Indian fig tree belongs to the family Cactaceae and was known as a medicinal plant for its rich source of bioactive substances. Objective: The present work aims to promote prickly pear seeds for traditional therapy by phenolic profiling and pharmacological tests of aqueous extract. Method: An analytical quantification was performed by UV-Visible and the identification of different bioactive compounds was done by HPLC-DAD. For pharmacological screening an in vivo evaluation of the various tests neuroleptic activity which consists of testing the recovery reflex; catatonic activity which is a test to detect catalepsy that can be characterized in animals by the administration of neuroleptic drugs; and for hypoglycemic activity a test was performed to assess glucose tolerance. Results: The administration of aqueous extract of the prickly pear seeds at a dose (400 mg/kg) allows a reduction in blood sugar with a maximum decrease of one and a half hours compared to the control group. Conclusion: This work makes it possible to postulate that the extract of prickly pear seeds is associated with a very interesting antihyperglycemic activity given its high content of phenolic compounds.