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.     

Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry,Ethnopharmacology, and Industrial Applications

Psidium guajava L. (guava) is a small tree known for its fruit flavor that is cultivated almost around the globe in tropical areas. Its fruit is amazingly rich in antioxidants, vitamin C, potassium, and dietary fiber. In different parts of the world, this plant holds a special place with respect to fruit and nutritional items. Pharmacological research has shown that this plant has more potential than just a fruit source; it also has beneficial effects against a variety of chronic diseases due to its rich nutritional and phytochemical profile. The primary goal of this document is to provide an updated overview of Psidium guajava L. and its bioactive secondary metabolites, as well as their availability for further study, with a focus on the health benefits and potential industrial applications. There have been several studies conducted on Psidium guajava L. in relation to its use in the pharmaceutical industry. However, its clinical efficacy and applications are still debatable. Therefore, in this review a detailed study with respect to phytochemistry of the plant through modern instruments such as GC and LC-MS has been discussed. The biological activities of secondary metabolites isolated from this plant have been extensively discussed. In order to perform long-term clinical trials to learn more about their effectiveness as drugs and applications for various health benefits, a structure activity relationship has been established. Based on the literature, it is concluded that this plant has a wide variety of biopharmaceutical applications. As a whole, this article calls for long-term clinical trials to obtain a greater understanding of how it can be used to treat different diseases.     

DAD-Net: Classification of Alzheimer’s Disease Using ADASYN Oversampling Technique and Optimized Neural Network

Alzheimer’s Disease (AD) is a neurological brain disorder that causes dementia and neurological dysfunction, affecting memory, behavior, and cognition. Deep Learning (DL), a kind of Artificial Intelligence (AI), has paved the way for new AD detection and automation methods. The DL model’s prediction accuracy depends on the dataset’s size. The DL models lose their accuracy when the dataset has an imbalanced class problem. This study aims to use the deep Convolutional Neural Network (CNN) to develop a reliable and efficient method for identifying Alzheimer’s disease using MRI. In this study, we offer a new CNN architecture for diagnosing Alzheimer’s disease with a modest number of parameters, making it perfect for training a smaller dataset. This proposed model correctly separates the early stages of Alzheimer’s disease and displays class activation patterns on the brain as a heat map. The proposed Detection of Alzheimer’s Disease Network (DAD-Net) is developed from scratch to correctly classify the phases of Alzheimer’s disease while reducing parameters and computation costs. The Kaggle MRI image dataset has a severe problem with class imbalance. Therefore, we used a synthetic oversampling technique to distribute the image throughout the classes and avoid the problem. Precision, recall, F1-score, Area Under the Curve (AUC), and loss are all used to compare the proposed DAD-Net against DEMENET and CNN Model. For accuracy, AUC, F1-score, precision, and recall, the DAD-Net achieved the following values for evaluation metrics: 99.22%, 99.91%, 99.19%, 99.30%, and 99.14%, respectively. The presented DAD-Net outperforms other state-of-the-art models in all evaluation metrics, according to the simulation results.     

Fabrication of PEGylated Chitosan Nanoparticles Containing Tenofovir Alafenamide: Synthesis and Characterization

Tenofovir alafenamide (TAF) is an antiretroviral (ARV) drug that is used for the management and prevention of human immunodeficiency virus (HIV). The clinical availability of ARV delivery systems that provide long-lasting protection against HIV transmission is lacking. There is a dire need to formulate nanocarrier systems that can help in revolutionizing the way to fight against HIV/AIDS. Here, we aimed to synthesize a polymer using chitosan and polyethylene glycol (PEG) by the PEGylation of chitosan at the hydroxyl group. After successful modification and confirmation by FTIR, XRD, and SEM, TAF-loaded PEGylated chitosan nanoparticles were prepared and analyzed for their particle size, zeta potential, morphology, crystallinity, chemical interactions, entrapment efficacy, drug loading, in vitro drug release, and release kinetic modeling. The fabricated nanoparticles were found to be in a nanosized range (219.6 nm), with ~90% entrapment efficacy, ~14% drug loading, and a spherical uniform distribution. The FTIR analysis confirmed the successful synthesis of PEGylated chitosan and nanoparticles. The in vitro analysis showed ~60% of the drug was released from the PEGylated polymeric reservoir system within 48 h at pH 7.4. The drug release kinetics were depicted by the Korsmeyer–Peppas release model with thermodynamically nonspontaneous drug release. Conclusively, PEGylated chitosan has the potential to deliver TAF from a nanocarrier system, and in the future, cytotoxicity and in vivo studies can be performed to further authenticate the synthesized polymer.     

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds’ complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70–80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40–60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography–mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.     

Microscale Thermophoresis and Molecular Modelling to Explore the Chelating Drug Transportation in the Milk to Infant

The microscale thermophoresis (MST) technique was utilized to investigate lactoferrin–drug interaction with the iron chelator, deferiprone, using label-free system. MST depends on the intrinsic fluorescence of one interacting partner. The results indicated a significant interaction between lactoferrin and deferiprone. The estimated binding constant for the lactoferrin–deferiprone interaction was 8.9 × 10⁻⁶ ± 1.6, SD, which is to be reported for the first time. Such significant binding between lactoferrin and deferiprone may indicate the potentiation of the drug secretion into a lactating mother’s milk. The technique showed a fast and simple approach to study protein–drug interaction while avoiding complicated labeling procedures. Moreover, the binding behavior of deferiprone within the binding sites of lactoferrin was investigated through molecular docking which reflected that deferiprone mediates strong hydrogen bonding with ARG121 and ASP297 in pocket 1 and forms H-bond and ionic interaction with ASN640 and ASP395, respectively, in pocket 2 of lactoferrin. Meanwhile, iron ions provide ionic interaction with deferiprone in both of the pockets. The molecular dynamic simulation further confirmed that the binding of deferiprone with lactoferrin brings conformational changes in lactoferrin that is more energetically stable. It also confirmed that deferiprone causes positive correlation motion in the interacting residues of both pockets, with strong negative correlation motion in the loop regions, and thus changes the dynamics of lactoferrin. The MM-GBSA based binding free energy calculation revealed that deferiprone exhibits ∆G TOTAL of −63,163 kcal/mol in pocket 1 and −63,073 kcal/mol in pocket 2 with complex receptor–ligand difference in pocket 1 and pocket 2 of −117.38 kcal/mol and −111.54 kcal/mol, respectively, which in turn suggests that deferiprone binds more strongly in the pocket 1. The free energy landscape of the lactoferrin–deferiprone complex also showed that this complex remains in a high energy state that confirms the strong binding of deferiprone with the lactoferrin. The current research concluded that iron-chelating drugs (deferiprone) can be transported from the mother to the infant in the milk because of the strong attachment with the lactoferrin active pockets.     

Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of −32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.