α-Fluorocarbonyl compounds bearing a fluorine atom at the α-position relative to the carbonyl group have several important applications in medicinal, agrochemical, and biological chemistry. Herein, we report a simple and regioselective one-pot protocol for the side-chain α-fluorination of acetophenone derivatives. Utilizing a Fe(NO3)3∙9H2O/KBr and TBAF (1 M solution in THF) reagent mixture, the reaction delivers the corresponding α-fluorinated ketones in moderate to good yields (35–72
The development of strategies for oxidative fluorination represents an important avenue in the synthesis of valuable fluorine-containing compounds. A simple and regioselective methodology has been developed for the synthesis of 3,7-difluorinatedoxindole derivatives from 3-substituted indoles in a Selectfluor (TM)-mediated process in 15-71% yield. The reaction proceeds under mild, metal-free conditions with broad substrate scope and functional group tolerance, including electron-donating and electron-withdrawing groups on the indole ring
An attempt was made to use friction stir processing, a manufacturing technique usually employed for the fabrication of nanocomposites. For the substrate, AA7075 was used and for dispersed phase, B4C nanoparticles of size (<30 nm) were selected. Nanocomposite samples were fabricated using three different tool rotation speeds of 1000, 1200, and 1400 rpm, by keeping other process parameters as constant, and their influence on the nanocomposite was judged by the study of tribological behavior and microhardness. This research work aims at the self-assembled monolayer formation of B4C nanoparticles homogeneous layer into a substrate material and hence minimizing the quantity of nanoparticles required in the preparation of nanocomposites via FSP. The results in terms of increased microhardness compared to the substrate material are reflected by the sample processed at the tool rotation of 1200 rpm. The average microhardness was found out to be 195 Hv compared to the substrate material. There is a maximum increment attained in wear resistance upto 46.7% in the sample processed at 1200 rpm. Worn out surface morphology were analyzed through scanning electron microscopy, and X-ray diffraction was also undertaken to analyze the presence of reinforcement particle in the fabricated nanocomposites.
Experimental density (ρ) and viscosity (η) data were measured for binary mixtures of the ionic liquid [BMIM][NTf₂] with 2-methoxyethanol over the full composition range at temperatures from 298.15 to 323.15 K and atmospheric pressure. Excess molar volumes (Vᴱ) and viscosity deviations (Δη) were derived to assess mixture non-ideality. Density increases with ionic liquid mole fraction and decreases slightly with temperature. Negative Vᴱ values across most compositions indicate strong attractive interactions and efficient molecular packing. Viscosity rises markedly with ionic liquid content and decreases with temperature, while predominantly negative Δη values confirm significant non-ideal flow behavior due to specific intermolecular interactions. The combined volumetric and transport property data provide valuable insight into the molecular interactions governing the thermophysical behavior of [BMIM][NTf₂]–2ME mixtures and are expected to be useful for the design and optimization of ionic-liquid-based solvent systems in industrial and environmental applications.
OBJECTIVES:The study aimed to explore the crucial genes involved in cancer-related biological processes, including EMT, autophagy, apoptosis, anoikis, and metastasis. It also sought to identify common genes among the pathways linked to these biological processes, determine the level of Bcl-2 expression in various types of cancers, and find a potent inhibitor of Bcl-2 among natural compounds. METHODS:Common genes involved in the pathways related to EMT, autophagy, apoptosis, anoikis, and metastasis were explored, and the level of the most frequently overexpressed gene that was Bcl-2, in various types of cancers was analyzed by gene expression analysis. A set of 102 natural compounds was sorted according to their docking scores using molecular docking and filtering. The top-ranked molecule was chosen for additional molecular dynamics (MD) simulation for 100 ns. Differential gene expression analysis was performed for Dioscin using GEO2R. RESULTS:The study identified four common genes, Bcl-2, Bax, BIRC3, and CHUK, among the pathways linked to EMT, autophagy, apoptosis, anoikis, and metastasis. Bcl-2 was highly overexpressed in many cancers, including Acute Myeloid Leukemia, Diffuse large B cell lymphoma, and Thymoma. The Dioscin structure in the Bcl-2 binding site received the highest docking score and the most relevant interactions. Dioscin's determined binding free energy by MM/GBSA was -52.21 kcal/mol, while the same calculated by MM/PBSA was -9.18 kcal/mol. A p-value of less than 0.05 was used to determine the statistical significance of the analysis performed using GEO2R. It was observed that Dioscin downregulates Bcl-2, BIRC3, and CHUK and upregulates the pro-apoptotic protein Bax. CONCLUSION:The study concluded that Dioscin has the potential to act as a protein inhibitor, with a noteworthy value of binding free energy and relevant interactions with the Bcl-2 binding site. Dioscin might be a good alternative for targeting multiple cancer pathways through a single target.
Nanotechnology has provided an enabling platform for innovations in site-specific cancer therapy and personalized oncomedicine. One of the most important advances in this area is the creation of nanomedicines that target cancer cells, which facilitates the progress of precise therapeutic interventions. Efficient drug delivery into tumor cells remains one of the critical challenges in cancer therapy. However, cancer-cell-targeted nanomedicines that function within the intricate milieu of the tumor microenvironment have shown potential to improve therapeutic efficiency. Epigallocatechin gallate (EGCG), the major phytochemical in Phyllanthus emblica (amla), is known for its anticancer and anti-inflammatory properties. In this study, we developed pH-responsive calcium carbonate nanoparticles (CCNPs) as a nanocarrier for EGCG to enhance its intracellular delivery and therapeutic efficacy. EGCG was physically adsorbed onto the surface of CCNPs. The synthesized nanoparticles were characterized using UV–visible spectroscopy, scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential analysis, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). In-vitro drug release studies demonstrated a sustained and more prominent release of EGCG at the acidic pH (4.8) typical of the tumor microenvironment. The biological activity of EGCG-loaded CCNPs was evaluated using the MTT assay and apoptosis analysis. The results showed significant cytotoxicity against colorectal cancer cells (COLO-320 DM), while blank CCNPs exhibited low toxicity and high biocompatibility. Intracellular uptake studies further confirmed the preferential accumulation of nanoparticles within colorectal cancer cells. Flow cytometry-based apoptosis assays revealed that EGCG-conjugated CCNPs induced considerable cancer cell death. These findings suggest that EGCG-loaded calcium carbonate nanoparticles may serve as an effective and biocompatible drug delivery platform for targeted colorectal cancer therapy.
Over the past few years, researchers have increased their focus on using functionalized and modified nanostructures in biomedical applications. Biomedical nanotechnology has a wide range of applications across a number of fields, including implant and tissue engineering, diagnosis, and treatment. Enhancing the surface properties of implants with nanobiomaterials could enhance their biocompatibility. Many medical implants and devices could not act as intended without these coatings. Nanomaterials are used for coatings, wound care, medical textiles, and the antimicrobial properties of these materials are used in cardiology (in stents), orthopedics (in joint replacement implants), and dentistry (in dental implants). As well as augmenting the effect of therapies, such as chemotherapy, nanomaterials can directly kill tumor cells at high temperatures, which can also enhance the effects of therapies. Medical implants and devices based on nanobiomaterials present a great prospect for enhancing the performance and effectiveness of the device, and this has become a growing field. Nanotechnology is being applied in new ways to assist in treating different diseases, and this perspective hopes to provide new understandings of how it can be best applied to this purpose.
Autophagy, a highly regulated cellular process, assumes a dual role in the context of cancer. On the one hand, it functions as a crucial homeostatic pathway, responsible for degrading malfunctioning molecules and organelles, thereby maintaining cellular health. On the other hand, its involvement in cancer development and regression is multifaceted, contingent upon a myriad of factors. This review meticulously examines the intricacies of autophagy, from its molecular machinery orchestrated by Autophagy-Related Genes (ATG) initially discovered in yeast to the various modes of autophagy operative within cells. Beyond its foundational role in cellular maintenance, autophagy reveals context-specific functions in processes like angiogenesis and inflammation. Our analysis delves into how autophagy-related factors directly impact inflammation, underscoring their profound implications for cancer dynamics. Additionally, we extend our inquiry to explore autophagy’s associations with cardiovascular conditions, neurodegenerative disorders, and autoimmune diseases, illuminating the broader medical relevance of this process. Furthermore, this review elucidates how autophagy contributes to sustaining hallmark cancer features, including stem cell maintenance, proliferation, angiogenesis, metastasis, and metabolic reprogramming. Autophagy emerges as a pivotal process that necessitates careful consideration in cancer treatment strategies. To this end, we investigate innovative approaches, ranging from enzyme-based therapies to MTOR inhibitors, lysosomal blockers, and nanoparticle-enabled interventions, all aimed at optimizing cancer treatment outcomes by targeting autophagy pathways. In summary, this comprehensive review provides a nuanced perspective on the intricate and context-dependent role of autophagy in cancer biology. Our exploration not only deepens our understanding of this fundamental process but also highlights its potential as a therapeutic target. By unraveling the complex interplay between autophagy and cancer, we pave the way for more precise and effective cancer treatments, promising better outcomes for patients.
The presence of one or more fluorine atoms in six-membered nitrogen heterocycles significantly impacts their chemical and physical properties, making them important in various applications, including pharmaceuticals and agrochemicals. This review, therefore, surveys the recent advances (mostly from 2010 onwards) in the synthesis of fluorinated six-membered N-heterocyclic compounds, including both the use of fluorinated starting materials and the introducing of fluorine atoms in the heterocyclic core and in either case exploring the benefits of microwave-assisted processes.
The fluorinated 5-membered N-containing heterocyclic compounds have wide utility in varied fields. The importance of these compounds has encouraged researchers to explore environment-friendly synthetic techniques for their synthesis. In this context, microwave-assisted synthesis has proved beneficial for the synthesis of fluorinated 5-membered N-heterocycles in an environmentally benign and energy-efficient manner. Compared to conventional heating, it offers several advantages, including quick heating, short reaction times, higher yields, and fewer side reactions. This article highlights the microwave-assisted fluorination of 5-membered N-heterocyclic compounds along with the synthesis of fluorinated 5-membered N-heterocyclic compounds using fluorinated starting materials. Microwave heating has revolutionized the field of fluorinated 5-membered nitrogen-heterocycles synthesis, offering significant advantages over traditional heating methods. This method promotes uniform heat dispersion, and faster and more selective reactions, while directly heating the reaction mixture. MW has been successfully employed for fluorination, cyclization, condensation, elimination, and substitution in synthesizing fluorinated 5-membered nitrogen heterocycles. image
Graphene possesses numerous exceptional and promising physical, chemical, and mechanical characteristics, making it a compelling candidate for a wide array of therapeutic applications. These applications span from basic drug or gene delivery systems to a diverse platform of multiple therapeutic modalities, comprising tissue engineering and cancer therapies. Graphene is a valuable scaffold in tissue engineering and has potential in photomedicine for wound healing and cancer therapy due to its photosensitizing properties. Graphene and its derivatives are currently being tested as carriers of therapeutic agents for cells or tissues, both in vivo and in vitro. These nanocarriers can have therapeutic effects which are influenced by various microenvironments. These include elevated glutathione and acidic pH as endogenous stimuli, and ultrasonic or light signals as exogenous stimuli. Graphene-based materials have paved the way for drug delivery and tumour treatment therapies due to their unique features and responsiveness. This chapter highlights the properties and unique structure of graphene that make it ideal for therapeutics. It also embodies a better and clearer understanding of therapeutic covering drug delivery, tissue engineering, gene delivery, several cancer therapies photodynamic therapy (PDT), radiotherapy (RT), photothermal therapy (PTT), etc. In this emerging field, we have discussed the significant challenges that need to be addressed, and we have also talked about the future prospects that it holds.
The study aims to discuss the challenges associated with treating prostate cancer (PCa), which is known for its complexity and drug resistance. It attempts to find differentially expressed genes (DEGs), such as those linked to anoikis resistance and circulating tumor cells, in PCa samples. This study involves analyzing the functional roles of these DEGs using gene enrichment analysis, and then screening of 102 bioactive compounds to identify a combination that can control the expression of the identified DEGs. In this study, 53 DEGs were identified from PCa samples including anoikis-resistant PCa cells and circulating tumor cells in PCa. Gene enrichment analysis with regards to functional enrichment of DEGs was performed. An inclusive screening process was carried out among 102 bioactive compounds to identify a combination capable of affecting and regulating the expression of selected DEGs. Eventually, gastrodin, nitidine chloride, chenodeoxycholic acid, and bilobalide were selected, as their combination demonstrated ability to modulate expression of 50 out of the 53 genes targeted. The subsequent analysis focused on investigating the biological pathways and processes influenced by this combination. The findings revealed a multifaceted and multidimensional approach to tumor regression. The combination of bioactive compounds exhibited effects on various genes including those related to production of inflammatory cytokines, cell proliferation, autophagy, apoptosis, angiogenesis, and metastasis. The current study has made a valuable contribution to the development of a combination of bioactive natural compounds that can significantly impede the development of treatment resistance in prostate tumor while countering the tumors’ evasion of the immune system. The implications of this study are highly significant as it suggests the creation of an enhanced immunotherapeutic, natural therapeutic concoction with combinatorial potential.
In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms. This altered nature can be attributed to their unique physicochemical profile. They can adversely affect human health and the environment. Nanomaterials that have been released into the environment tend to accumulate over time and can cause a significant impact on the ecosystem and organisms with adverse health effects. Increased use of nanoparticles has led to increased human exposure in their daily lives, making them more vulnerable to nanoparticle toxicity. Because of their small size, nanomaterials can readily cross biological membranes and enter cells, tissues, and organs. Therefore, the effect of nanomaterials on the human environment is of particular concern. The toxicological effects of nanomaterials and their mechanisms of action are being researched worldwide. Technological advances also support monitoring new nanomaterials marketed for industrial and household purposes. It is a challenging area because of the exceptional physicochemical properties of nanomaterials. This updated review focuses on the diverse toxicological perspective of nanomaterials. We have discussed the use of different types of nanoparticles and their physiochemical properties responsible for toxicity, routes of exposure, bio-distribution, and mechanism of toxicity. The review also includes various in vivo and in vitro methods of assessing the toxicity of nanomaterials. Finally, this review will provide a detailed insight into nano material-induced toxicological response, which can be beneficial in designing safe and effective nanoparticles.
Nanoparticles, nowadays, are being used in multiple applications such as therapeutics, industries, healthcare, cosmetics, and wound healing. Nanoparticles are entirely distinct from bulk particles as they have a giant surface area to volume ratio, therefore, showing various mechanical, electrical, physical, chemical, and optical properties, and thus, being used in different properties. As there are so many applications of metallic nanoparticles, there is a requirement for an efficient method for nanoparticle synthesis because the conventional chemical methods used to synthesize nanoparticles have limitations such as high cost and negative environmental impact. To overcome these drawbacks, green methods for nanoparticle synthesis have emerged as an eco-friendly and cost-efficient alternative. The green method for nanoparticle amalgam is cost-efficient and eco-friendly, unlike the chemical technique for nanoparticle synthesis. A variety of dimensions of nanoparticles can be synthesized by a substitute of the plant’s extract. Moreover, there is no requirement for external stabilizing agents and the involvement of harmful chemicals. This review aims to investigate how plant compounds can be used to synthesize silver nanoparticles and to evaluate the potential of plant extracts as reducing and stabilizing agents in the green synthesis of metallic nanoparticles. This review seeks to investigate the green production of metallic nanoparticles using plant-derived chemicals and to assess the potential of plant extracts as reducing and stabilizing agents. The study investigates the function of numerous plant substances in the synthesis process, such as flavonoids, alkaloids, terpenoids, saponins, and phenols. The paper also examines various methods for figuring out the morphology of nanoparticles created from various plant parts and their prospective uses as antibacterial agents, wastewater treatment, and reactive oxygen species modulators. This review offers insightful information about the possible uses of metallic nanoparticles by highlighting the advantages of environmentally friendly processes for the manufacture of silver nanoparticles.
Within the tumor microenvironment, the fight between the immune system and cancer influences tumor transformation. Metastasis formation is an important stage in the progression of cancer. This process is aided by cellular detachment and resistance to anoikis, which are achieved by altering intercellular signaling. Autophagy, specifically pro-survival autophagy, aids cancer cells in developing treatment resistance. Numerous studies have shown that autophagy promotes tumor growth and resistance to anoikis. To regulate protective autophagy, cancer-related genes phosphorylate both pro- and anti-apoptotic proteins. Apoptosis, a type of controlled cell death, eliminates damaged or unwanted cells. Anoikis is a type of programmed cell death in which cells lose contact with the extracellular matrix. The dysregulation of these cellular pathways promotes tumor growth and spread. Apoptosis, anoikis, and autophagy interact meticulously and differently depending on the cellular circumstances. For instance, autophagy can protect cancer cells from apoptosis by removing cellular components that are damaged and might otherwise trigger apoptotic pathways. Similarly, anoikis dysregulation can trigger autophagy by causing cellular harm and metabolic stress. In order to prevent or treat metastatic disease, specifically, targeting these cellular mechanisms may present a promising prospect for cancer therapy. This review discourses the state of our understanding of the molecular and cellular mechanisms underlying tumor transformation and the establishment of metastatic tumors. To enhance the prognosis for cancer, we highlight and discuss potential therapeutic approaches that target these processes and genes involved in them.
Cancer is a leading cause of mortality worldwide, and various anticancer medications have been developed that target different biological pathways involved in cancer growth and progression. Topoisomerase 1 (Top1) is an essential enzyme involved in unwinding supercoiled DNA, and it serves as a key target for several anti-cancer drugs. Irinotecan (FDA approved drug), a semi-synthetic camptothecin derivative, is an effective Top1 toxin that eliminates human cancer cells. Cancer patients suffer from the cholinergic syndrome caused by irinotecan and other Top1 inhibitors. Irinotecan-treated patients have developed cholinergic syndrome due to acetylcholinesterase (AChE) enzyme inhibition. It appears that irinotecan or its metabolites directly interact with AChE and inhibit its role of converting acetylcholine to choline, leading to an accumulation of acetylcholine and subsequent symptoms of the cholinergic syndrome. The phytochemicals present in Phyllanthus emblica, commonly referred to as amla, have been studied to determine their therapeutic effects. As an alternative treatment for cancer, this study explores the potential of phytochemicals found in amla to target and inhibit the Top1 protein. Additionally, the study aims to identify a non-inhibitor for AChE. Molecular docking studies assessed phytochemical binding affinities to Top1 and AChE enzymes, and ADME analyses were performed to assess their drug-likeness properties. Subsequently, molecular dynamic simulation was employed to assess the stability of these compounds. The results suggest that new anticancer medications that do not inhibit AChE or fresh Top1 inhibitors that use the camptothecin scaffold may alleviate some of the irinotecan's side effects.Communicated by Ramaswamy H. Sarma.
Polycyclic aromatic hydrocarbons (PAHs) are considered one of the major contaminants in the environment. The use of nanomaterials in the bioremediation of PAHs has received huge attention due to their physiochemical characteristics that arise as a result of nanoscale sizes. In bioremediation of PAHs, the use of nanomaterials has received immense attention because of their distinctive physicochemical characteristics, such as higher reactivity, greater surface area over the bulk counterparts, biocompatibility, and inert microenvironment. The effectiveness of nanomaterials in remediation of PAHs depends on the properties of the contaminated site and adaptation of nanomaterials to the site. Nanomaterials can be modified in a manner that will target the molecule of interest (contaminant) and that will raise the remediation efficacy. Titanium oxide and amphiphilic polyurethane nanoparticles are well explored for removal and degradation of hydrocarbon and other contaminants in wastewater, soil, etc. Polymeric-nanonetwork particles were found to increase solubilization and mineralization of a hydrophobic contaminant, phenanthrene, in a contaminated aquifer. Combining nanomaterials with biologic methods can help remove harmful contaminants more efficiently from the environment; for instance, along with Nocardiopsis MSA13A, iron nanoparticles are utilized in the bioremediation process. Based on inner and outer dimensions and phases of matter, nanomaterials can be classified as nanoobjects and nanostructures, based on one or more outer dimensions and surface or inner structure (in nanoscale), respectively. These classes of nanomaterials consist of nanoplates, nanofibers, composites, nanofoams, nanocrystals, nanotubes, etc. This chapter gives a comprehensive discussion on nanomaterials and remediation of PAHs from contaminated sites applying nanotechnology.
The world has witnessed the cruelty of COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association of COVID-19 with other secondary and bacterial co-infections has tremendously contributed to lung infections. An increased probability of having a secondary lung infection was observed among the post-COVID patients. The treatment of antibiotics has ameliorated the mortality rate. However, the stewardship of antibiotic treatment was linked to increased organ failure. Therefore, the paper discusses the interactions between the virus and host through the ACE2 receptors that contribute to COVID-19 development. Furthermore, the paper provides an invaluable compendium history of SARS-CoV-2 genomic composition. It revolves around most classes of antibiotics used to treat COVID-19 disease and post-COVID lung infections with the complete mechanism. This binds with the exertion of the antibiotics for bacterial infection associated with COVID-19 patients and how beneficial and effective responses have been recorded for the treatment. The application of nanotechnology and possible approaches of nanomedicines is also discussed to its potential usage.
Abstract In Indian cities, airborne particulate matter, PM 2.5 , is related with regional or across border problem and that of PM 10 with local-land urban problem. The present study was carried out for risk assessment of PM 10 and PM 2.5 and its associated carbonaceous component and heavy metals of an experimental agriculture farm site of Delhi, India. In our studies, at the agricultural site which is surrounded by heavy traffic and industries related sites, concentrations of both PM 10 and PM 2.5 varied significantly from 136.34 to 176.66 µg/m 3 and 56 to 162 µ/m 3 respectively. However, the concentrations of NOx were relatively higher during the months of February and March. The concentrations of O 3 in the present study, were observed to be the highest in February. In general, the Hazard index for both adults and children population was reported to be < 1, which indicated the probability of non-carcinogenic risks to both populations as negative.