Synthesis of Starch-Grafted Polymethyl Methacrylate via Free Radical Polymerization Reaction and Its Application for the Uptake of Methylene Blue

In this research, a new biodegradable and eco-friendly adsorbent, starch-grafted polymethyl methacrylate (St-g-PMMA) was synthesized. The St-g-PMMA was synthesized by a free radical polymerization reaction in which methyl methacrylate (MMA) was grafted onto a starch polymer chain. The reaction was performed in water in the presence of a potassium persulfate (KPS) initiator. The structure and different properties of the St-g-PMMA was explored by FT-IR, 1H NMR, TGA, SEM and XRD. After characterization, the St-g-PMMA was used for the removal of MB dye. Different adsorption parameters, such as effect of adsorbent dose, effect of pH, effect of initial concentration of dye solution, effect of contact time and comparative adsorption study were investigated. The St-g-PMMA showed a maximum removal percentage (R%) of 97% towards MB. The other parameters, such as the isothermal and kinetic models, were fitted to the experimental data. The results showed that the Langmuir adsorption and pseudo second order kinetic models were best fitted to experimental data with a regression coefficient of R² = 0.93 and 0.99, respectively.     

Macrophage-Targeted Punicalagin Nanoengineering to Alleviate Methotrexate-Induced Neutropenia: A Molecular Docking,DFT, and MD Simulation Analysis

Punicalagin is the most bioactive pomegranate polyphenol with high antioxidant and free-radical scavenging activity and can potentially cure different ailments related to the cardiovascular system. The current research work was envisioned to predict the targeting efficiency of punicalagin (PG) nanoparticles to the macrophages, more specifically to bone marrow macrophages. For this, we selected mannose-decorated PLGA-punicalagin nanoparticles (Mn-PLGA-PG), and before formulating this nanocarrier in laboratory settings, we predicted the targeting efficiency of this nanocarrier by in silico analysis. The analysis proceeded with macrophage mannose receptors to be acquainted with the binding affinity and punicalagin-based nanocarrier interactions with this receptor. In silico docking studies of macrophage mannose receptors and punicalagin showed binding interactions on its surface. PG interacted with hydrogen bonds to the charged residue ASP668 and GLY666 and polar residue GLN760 of the Mn receptor. Mannose with a docking score of −5.811 Kcal/mol interacted with four hydrogen bonds and the mannose receptor of macrophage, and in PLGA, it showed a −4.334 Kcal/mol docking score. Further, the analysis proceeded with density functional theory analysis (DFT) and HOMO–LUMO analysis, followed by an extensive 100 ns molecular dynamics simulation to analyse the trajectories showing the slightest deviation and fluctuation. While analysing the ligand and protein interaction, a wonderful interaction was found among the atoms of the ligand and protein residues. This computational study confirms that this nanocarrier could be a promising lead molecule to regulate the incidence of drug-induced neutropenia. Furthermore, experimental validation is required before this can be stated with complete confidence or before human use.     

Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active “constituent–target–pathway” networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense.     

Design,Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC₅₀ values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure–activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.     

On Some Topological Indices Defined via the Modified Sombor Matrix

Let G be a simple graph with the vertex set V={v1,…,vn} and denote by dvi the degree of the vertex vi. The modified Sombor index of G is the addition of the numbers (dvi2+dvj2)−1/2 over all of the edges vivj of G. The modified Sombor matrix AMS(G) of G is the n by n matrix such that its (i,j)-entry is equal to (dvi2+dvj2)−1/2 when vi and vj are adjacent and 0 otherwise. The modified Sombor spectral radius of G is the largest number among all of the eigenvalues of AMS(G). The sum of the absolute eigenvalues of AMS(G) is known as the modified Sombor energy of G. Two graphs with the same modified Sombor energy are referred to as modified Sombor equienergetic graphs. In this article, several bounds for the modified Sombor index, the modified Sombor spectral radius, and the modified Sombor energy are found, and the corresponding extremal graphs are characterized. By using computer programs (Mathematica and AutographiX), it is found that there exists only one pair of the modified Sombor equienergetic chemical graphs of an order of at most seven. It is proven that the modified Sombor energy of every regular, complete multipartite graph is 2; this result gives a large class of the modified Sombor equienergetic graphs. The (linear, logarithmic, and quadratic) regression analyses of the modified Sombor index and the modified Sombor energy together with their classical versions are also performed for the boiling points of the chemical graphs of an order of at most seven.     

Molecular Characterization of Bacterial Isolates from Soil Samples and Evaluation of their Antibacterial Potential against MDRS

Some soil microbes, with their diverse inhabitance, biologically active metabolites, and endospore formation, gave them characteristic predominance and recognition among other microbial communities. The present study collected ten soil samples from green land, agricultural and marshy soil sites of Khyber Pakhtunkhwa, Pakistan. After culturing on described media, the bacterial isolates were identified through phenotypic, biochemical and phylogenetic analysis. Our phylogenetic analysis revealed three bacterial isolates, A6S7, A1S6, and A1S10, showing 99% nucleotides sequence similarity with Brevibacillus formosus, Bacillus Subtilis and Paenibacillus dendritiformis. The crude extract was prepared from bacterial isolates to assess the anti-bacterial potential against various targeted multidrug-resistant strains (MDRS), including Acinetobacter baumannii (ATCC 19606), Methicillin-resistant Staphylococcus aureus (MRSA) (BAA-1683), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (BAA-2108), Staphylococcus aureus (ATCC 292013), Escherichia coli (ATCC25922) and Salmonella typhi (ATCC 14028). Our analysis revealed that all bacterial extracts possess activity against Gram-negative and Gram-positive bacteria at a concentration of 5 mg/mL, efficiently restricting the growth of E. coli compared with positive control ciprofloxacin. The study concluded that the identified species have the potential to produce antimicrobial compounds which can be used to control different microbial infections, especially MDRS. Moreover, the analysis of the bacterial extracts through GC-MS indicated the presence of different antimicrobial compounds such as propanoic acid, oxalic acid, phenol and hexadecanoic acid.     

Synthesis,Molecular Docking Study,and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety

Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea (2) was prepared and reacted with various hydrazonoyl halides 3a–h, α-haloketones 5a–d, 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a–h, 3-phenyl-4-arylthiazoles 6a–d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC₅₀ = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC₅₀ = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.     

Antibacterial Activity of Dental Composite with Ciprofloxacin Loaded Silver Nanoparticles

Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins.     

Cross-Linked Ionic Liquid Polymer for the Effective Removal of Ionic Dyes from Aqueous Systems: Investigation of Kinetics and Adsorption Isotherms

In the current study, we have synthesized an imidazolium based cross-linked polymer, namely, 1-vinyl-3-ethylimidazolium bis(trifluoromethylsulfonyl)imide (poly[veim][Tf₂N]-TRIM) using trimethylolpropane trimethacrylate as cross linker, and demonstrated its efficiency for the removal of two extensively used ionic dyes—methylene blue and orange-II—from aqueous systems. The detailed characterization of the synthesized poly[veim][Tf₂N]-TRIM was performed with the help of ¹H NMR, TGA, FT-IR and FE-SEM analysis. The concentration of dyes in aqueous samples before and after the adsorption process was measured using an UV-vis spectrophotometer. The process parameters were optimised, and highest adsorption was obtained at a solution pH of 7.0, adsorbent dosage of 0.75 g/L, contact time of 7 h and dye concentrations of 100 mg/L and 5.0 mg/L for methylene blue and orange-II, respectively. The adsorption kinetics for orange-II and methylene blue were well described by pseudo-first-order and pseudo–second-order models, respectively. Meanwhile, the process of adsorption was best depicted by Langmuir isotherms for both the dyes. The highest monolayer adsorption capacities for methylene blue and orange-II were found to be 1212 mg/g and 126 mg/g, respectively. Overall, the synthesized cross-linked poly[veim][Tf₂N]-TRIM effectively removed the selected ionic dyes from aqueous samples and provided >90% of adsorption efficiency after four cycles of adsorption. A possible adsorption mechanism between the synthesised polymeric adsorbent and proposed dyes is presented. It is further suggested that the proposed ionic liquid polymer adsorbent could effectively remove other ionic dyes and pollutants from contaminated aqueous systems.     

Cerium Oxide Nanorods Synthesized by Dalbergia sissoo Extract for Antioxidant,Cytotoxicity, and Photocatalytic Applications

In this study, cerium oxide nanorods (CeO₂-NRs) were synthesized by using the phytochemicals present in the Dalbergia sissoo extract. The physiochemical characteristics of the as-prepared CeO₂-NRs were investigated by using ultraviolet-visible spectroscopy (UV-VIS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction analysis (XRD). The SEM and UV-VIS analyses revealed that the acquired nanomaterials possessed a rod-like morphology while the XRD results further confirmed that the synthesized NRs exhibited a cubic crystal lattice system. The antioxidant capacity of the synthesized CeO₂-NRs was investigated by using several in vitro biochemical assays. It was observed that the synthesized NRs exhibited better antioxidant potential in comparison to the industrial antioxidant of the butylated hydroxyanisole (BHA) in 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The biochemical assays, including lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase activity (CAT), were also performed in the human lymphocytes incubated with the CeO₂-NRs to investigate the impact of the NRs on these oxidative biomarkers. Enhanced reductive capabilities were observed in all the assays, revealing that the NRs possess excellent antioxidant properties. Moreover, the cytotoxic potential of the CeO₂-NRs was also investigated with the MTT assay. The CeO₂-NRs were found to effectively kill off the cancerous cells (MCF-7 human breast cancer cell line), further indicating that the synthesized NRs exhibit anticancer potential as well. One of the major applications studied for the prepared CeO₂-NRs was performing the statistical optimization of the photocatalytic degradation reaction of the methyl orange (MO) dye. The reaction was optimized by using the technique of response surface methodology (RSM). This advanced approach facilitates the development of the predictive model on the basis of central composite design (CCD) for this degradation reaction. The maximum degradation of 99.31% was achieved at the experimental optimized conditions, which corresponded rather well with the predicted percentage degradation values of 99.58%. These results indicate that the developed predictive model can effectively explain the performed experimental reaction. To conclude, the CeO₂-NRs exhibited excellent results for multiple applications.