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Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.
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Antineoplásicos , Isatina , Neoplasias Ovarianas , Humanos , Feminino , Isatina/farmacologia , Substâncias Intercalantes/farmacologia , Substâncias Intercalantes/química , Linhagem Celular Tumoral , Antineoplásicos/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , DNA/metabolismo , Relação Estrutura-AtividadeRESUMO
Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells. All of these inhibitors, however, are either ineffective, very toxic, or have yet to be subjected to rigorous testing on their effectiveness. Although various drug-like compounds targeting ALDH have been reported in the literature, none have made it to routine use in the oncology clinic. As a result, new potent, non-toxic, bioavailable, and therapeutically effective ALDH inhibitors are still needed. In this study, we designed and synthesized potent multi-ALDH isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500 nM. Compound 3 was also the most cytotoxic to cancer cells, with an IC50 in the range of 2.1 to 3.8 µM for ovarian, colon, and pancreatic cancer cells, compared to normal and embryonic kidney cells (IC50 7.1 to 8.7 µM). Mechanistically, compound 3 increased ROS activity due to potent multi-ALDH isoform inhibition, which increased apoptosis. Taken together, this study identified a potent multi-isoform ALDH inhibitor that could be further developed as a cancer therapeutic.
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Aldeído Desidrogenase , Inibidores Enzimáticos , Isatina , Simulação de Acoplamento Molecular , Humanos , Isatina/química , Isatina/farmacologia , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído Desidrogenase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura MolecularRESUMO
Physicochemical properties of water influence planktonic diversity and distribution, which is essential in obtaining basic knowledge of aquatic biodiversity. Thus current study aims to investigate the spatiotemporal diversity, abundance ratio, and distribution of phytoplankton species and their association with water quality parameters of Chashma Lake, Pakistan. During the study period from 2018 to 2019, we measured 13 physicochemical parameters across three selected sampling sites (S1, S2, and S3) in Chashma Lake, revealing both spatial and temporal variability. Dissolved oxygen (DO) was higher in S3, while S1 exhibited higher alkalinity levels, carbon dioxide, phosphorus, and chloride levels. The study identified 77 phytoplankton species grouped into five taxonomic categories, with Cyanobacteria dominating (39.90%), followed by Chlorophyta (33.4%) and Bacillariophyta (24.88%). Euglenozoa and Ochrophyta were less abundant (1.3% and 0.41%, respectively). Spatial variations in phytoplankton distribution were noted, with Chlorophyta being more abundant at S2, Bacillariophyta and Cyanobacteria at S1, and Euglenozoa dominating at S3. Canonical Correspondence Analysis (CCA) revealed the influence of various physicochemical parameters on phytoplankton distribution. This comprehensive study provides valuable insights for the ecological assessment and monitoring of water bodies. It is recommended that continuous monitoring is required to capture long-term trends, further explore the specific environmental drivers impacting phytoplankton dynamics, and consider management strategies for maintaining water quality and biodiversity in Chashma Lake.
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Biodiversidade , Monitoramento Ambiental , Lagos , Fitoplâncton , Lagos/química , Paquistão , Rios/química , Cianobactérias/crescimento & desenvolvimento , Fósforo/análise , Qualidade da ÁguaRESUMO
BACKGROUND: To establish the risk of catching COVID-19 as urology emergency inpatient and assess patients' fears and attitudes towards seeking help. METHODS: A single-centre retrospective study of urological emergency admissions was conducted over a 10-week period in 2019 and compared to same period of 2020 pandemic. Also, a telephone survey was performed based on a COVID-19 fear questionnaire. RESULTS: In-hospital, infection rate was 0.82% during or within 28 days of discharge with no related mortality. The majority of patients were afraid to visit A&E during the pandemic with less being afraid to visit their GPs; 64% were reluctant to seek medical input by trying self-treatment; 56% admitted intentional delay to visit the hospital. Additionally, 56% considered risk of getting COVID-19 was higher rather than leaving their condition untreated. Interestingly, the vast majority (82%) stated that they would not change approach regarding hospital visits if the same situation occurred. CONCLUSIONS: The risk of contracting COVID 19 while a urology in patient in a COVID-19 epicentre was very low with no COVID-19-related mortality. Our data support that patients should be encouraged to attend rather than stay at home during future surges in the pandemic to prevent further non-COVID-19-related harm.
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COVID-19 , Humanos , COVID-19/epidemiologia , Estudos Retrospectivos , Hospitais , Medo , Reino Unido/epidemiologiaRESUMO
Superior mesenteric artery (SMA) aneurysm is a rare disease, especially if it is mycotic (infective) in origin. It is difficult to detect the problem during its initial natural course and usually presents in late phase due to its complications such as rupture, dissection, haemorrhage, and mesenteric ischaemia. Initially, the patient present with non-specific symptoms like vague colicky abdominal pain, nausea, vomiting, discomfort, malaise, and low-grade fever but prompt workup and intervention can lead to definitive diagnosis and uneventful outcome. This report describes the case of a 60-year-old male patient who presented with non-specific abdominal symptoms and, on workup, was diagnosed with superior mesenteric artery mycotic aneurysm. It was successfully treated surgically by resection of aneurysm and reconstruction of superior mesenteric artery by inter-positional Polytetrafluoroethylene (PTFE) synthetic vascular graft.
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Aneurisma Infectado , Gastroenteropatias , Isquemia Mesentérica , Masculino , Humanos , Pessoa de Meia-Idade , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/cirurgia , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/cirurgia , AbdomeRESUMO
The ability to develop novel medications based on nanoscale complexes has greatly enhanced the capabilities of current pharmaceuticals and has made multidimensional research of these complexes extremely relevant in recent years. Selenium nanoparticles (SeNPs) constitute one such example which in general, could be created by biological, chemical, and physical techniques. Biogenic SeNPs show improved compatibility with human organs and tissues. While sufficient levels of selenium (Se) are crucial for triggering immunity, they also play a role in controlling exaggerated immunological responses and persistent inflammation. More significantly, SeNPs can activate the immune systems, both innate and adaptive, in the tumor microenvironment, which results in an immunological response that fights various diseases caused by chronic inflammation. In this article, we discuss the functions of Se and SeNPs in controlling inflammation with particular emphasis given to their role in combating inflammation in different diseases. Finally, even though Se status exhibits considerable promise as a reliable indicator of autoimmune and inflammatory diseases, novel functionalized SeNPs may likely offer a more effective and reliable tool in both disease prevention and treatment.
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Nanopartículas , Selênio , Humanos , Selênio/uso terapêutico , Inflamação , Microambiente Tumoral , Preparações FarmacêuticasRESUMO
Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.
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Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Vitanolídeos/química , Vitanolídeos/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Desenho de Fármacos , Descoberta de Drogas , Humanos , Vitanolídeos/síntese química , Vitanolídeos/farmacologiaRESUMO
Digital rectal examination (DRE) is routinely performed as part of a urology clinical assessment in patients with a clinical suspicion of prostate cancer. An abnormal DRE or a raised prostate specific antigen (PSA) level are part of the criteria for primary care referral to secondary care due to a suspicion of prostate cancer. The current Coronavirus-19 (COVID-19) pandemic has resulted in the rapid adoption of virtual consultations in the form of telephone or video consultations making clinical examination difficult. In the case of prostate cancer diagnostic pathways, often clinicians now rely on PSA measurements and MRI, where radiological services are available, without the requirement for a DRE. We discuss the limited role DRE has in the modern prostate cancer diagnostic pathway due to the widespread adoption of MRI particularly in the COVID-19 era.
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Exame Retal Digital , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , COVID-19 , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , SARS-CoV-2RESUMO
We previously found that km23-1/DYNLRB1 is required for transforming growth factor-ß (TGFß) production through Ras/ERK pathways in TGFß-sensitive epithelial cells and in human colorectal cancer (CRC) cells. Here we demonstrate that km23-1/DYNLRB1 is required for mitogen-activated protein kinase kinase (MEK) activation in human CRC cells, detected by km23-1/DYNLRB1-siRNA inhibition of phospho-(p)-MEK immunostaining in RKO cells. Furthermore, we show that CRISPR-Cas9 knock-out (KO) of km23-1/DYNLRB1 reduced cell migration in two additional CRC models, HCT116 and DLD-1. Of interest, in contrast to our previous work showing that dynein motor activity was required for TGFß-mediated nuclear translocation of Smad2, in the current report, we demonstrate for the first time that disruption of dynein motor activity did not reduce TGFß-mediated activation of MEK1/2 or c-Jun N-terminal kinase (JNK). Moreover, size exclusion chromatography of RKO cell lysates revealed that B-Raf, extracellular signal-regulated kinase (ERK), and p-ERK were not present in the large molecular weight fractions containing dynein holocomplex components. Furthermore, sucrose gradient fractionation of cell lysates from both HCT116 and CBS CRC cells demonstrated that km23-1/DYNLRB1 co-sedimented with Ras, p-ERK, and ERK in fractions that did not contain components of holo-dynein. Thus, km23-1/DYNLRB1 may be associated with activated Ras/ERK signaling complexes in cell compartments that do not contain the dynein holoprotein complex, suggesting dynein-independent km23-1/DYNLRB1 functions in Ras/ERK signaling. Finally, of the Ras isoforms, R-Ras is most often associated with cell migration, adhesion, and protrusive activity. Here, we show that a significant fraction of km23-1/DYNLRB1 and RRas wase co-localized at the protruding edges of migrating HCT116 cells, suggesting an important role for the km23-1/DYNLRB1-R-Ras complex in CRC invasion.
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New indole-tethered [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (8a-j) and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) were synthesized using [4+2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with indole-ketenes. All molecular hybrids were structurally characterized by spectroscopic techniques (IR, NMR, and HRMS) and screened for their anti-pancreatic cancer activity in vitro. The [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) showed stronger anti-pancreatic cancer activity than the [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrids (8a-j) against the PANC-1 cell line. Compound 9d bearing an ortho-chlorophenyl moiety emerged as the most potent anti-pancreatic cancer agent with an IC50 value of 7.7 ± 0.4 µM, much superior to the standard drug Gemcitabine (IC50 > 500 µM). The discovery of these [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids elicits their potentials as pursuable candidates for pancreatic cancer chemotherapy.
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Antineoplásicos/farmacologia , Indóis/farmacologia , Oxidiazóis/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Pirimidinas/farmacologia , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/química , Estrutura Molecular , Oxidiazóis/química , Neoplasias Pancreáticas/patologia , Pirimidinas/química , Relação Estrutura-Atividade , Tiadiazóis/químicaRESUMO
BACKGROUND: The Escherichia coli cytosine deaminase (CD)/5-fluorocytosine (5-FC) approach emerges as a potential aid for suicide gene therapy in the field of modern cancer treatment. However, the poor binding affinity of CD towards 5-FC compared to the natural substrate cytosine limits its application for successful suicide gene therapy. Redesigning a bacterial mutant CD with site-directed mutagenesis showed higher potency compare to wild-type CD (wtCD) in vitro. In the present study, we conducted a comparative analysis of F186W mutant and wtCD in a human lung cancer cell line (A549). METHODS AND RESULTS: A comparative investigation was initiated with cell viability analyses by MTT and trypan blue dye exclusion assays on A549 cells transfected with wtCD and F186W genes. The mode of cell death was confirmed by acridine Orange/ethidium Bromide dual staining. Furthermore, flow cytometric assessments were performed by cell cycle analysis and caspase 3 assay. The experimental results showed a drug dependent decrease in cell viability; interestingly, mutant (F186W) reached IC50 at a much lower concentration of prodrug (5-FC) than wtCD. Cell cycle analysis showed that G1 arrest of a larger population of 5-FC treated F186W transfected cells, in contrast to that of wtCD under similar conditions. The caspase 3 assay revealed progression and execution of apoptosis. CONCLUSIONS: We report a novel bacterial CD mutant that provided a superior alternate to the wtCD suicide gene. The F186W mutant required a much lower dose of 5-FC to reach its IC50 , thus minimizing the systemic side effects of large doses of 5-FC as required for wtCD.
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Citosina Desaminase/genética , Proteínas de Escherichia coli/genética , Escherichia coli/enzimologia , Terapia Genética , Apoptose/genética , Linhagem Celular Tumoral , Citosina Desaminase/uso terapêutico , Proteínas de Escherichia coli/uso terapêutico , Humanos , Neoplasias Pulmonares/terapia , Mutação , TransgenesRESUMO
BACKGROUND: Aberrant DNA methylation profiles are a characteristic feature of almost all types of cancers including hepatocellular carcinoma (HCC) and play an important role in carcinogenesis. In spite of the accumulating evidence that suggests appearance of such aberrations at precancerous stages, very little effort has been invested to investigate such possible methylation events in patients at risk of developing HCC i.e. those suffering from chronic hepatitis C virus (HCV) infection and liver cirrhosis (LC). We reasoned that such an analysis could lead to the identification of novel predictive biomarkers as well as potential drug targets. METHODS: Promoter methylation status of two Wnt inhibitors SFRP2 and DKK1 was quantitatively analyzed by bisulfite pyrosequencing in a series of liver biopsy samples. These biopsies were collected from HCV-infected individuals suffering from chronic hepatitis (CH; n = 15), liver cirrhosis (LC; n = 13) and hepatocellular carcinoma (HCC; n = 41). DNA isolated from infection free normal livers (N; n =10) was used as control. RESULTS: Our analysis revealed that both of the genomic loci were significantly hypermethylated in CH patients' livers as compared to normal controls (p = 0.0136 & 0.0084 for SFRP2 and DKK1, respectively; Mann-Whitney U test). DNA methylation levels for both loci were also significantly higher in all the diseased cohorts as compared to normal controls (p < 0.0001 and = 0.0011 for SFRP2 and DKK1, respectively; Kruskal-Wallis test). However, a comparison between three disease cohorts (CH, LC & HCC) revealed no significant difference in levels of DNA methylation at DKK1 promoter. In contrast, a progressive increase in DNA methylation levels was observed at the SFRP2 promoter (i.e. N < CH & LC < HCC). CONCLUSION: This study demonstrated that in HCV infected liver tissues hypermethylation at promoter regions of key cancer related genes SFRP2 and DKK1, appears early at CH and LC stages, long before the appearance of HCC.
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Carcinoma Hepatocelular/patologia , Metilação de DNA , Hepatite C Crônica/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Cirrose Hepática/patologia , Proteínas de Membrana/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Biópsia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Via de Sinalização WntRESUMO
The advancement of highly effective heterojunction photocatalysts with improved charge separation and transfer has become a crucial scientific perspective for utilizing solar energy. In this study, we developed the S-scheme heterostructure by depositing N-doped CeO2-δ (NC) nanoparticles onto two-dimensional ZnIn2S4 (ZIS) nanosheets via hydrolysis strategy for significantly enhanced photocatalytic hydrogen evolution reaction. The optimal H2 generation rate of â¼ 798 µmol g-1 h-1 was achieved for NC-3@ZIS under solar light irradiation, which is about 18 and 2 times higher than those of pristine CeO2 (â¼44 µmol g-1 h-1) and ZIS (â¼358 µmol g-1 h-1), respectively. The photogenerated electrons from NC interact with the photogenerated holes of ZIS driven by an internal electric field, confirmed by In-situ KPFM, DFT calculation, and XPS results. According to EPR and photoelectrochemical measurements, NC-3@ZIS composite shows dramatically high separation efficiency of photogenerated charge carriers. This study provides a new approach for developing non-noble metal S-scheme heterojunctions with enhanced photocatalytic hydrogen evolution.
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In this study, we synthesized novel, economically efficient phosphonic acid-functionalized grafted sepiolite nanohybrids for selective elimination of copper ions from water. These nanohybrids were prepared by graft polymerization of glycidyl methacrylate onto sepiolite. We utilized free radical graft polymerization to graft glycidyl methacrylate (GMA) onto silanized sepiolite. The nanohybrids obtained exhibited a grafting percentage of 479% at 0.3 g of KPS initiator, 15% GMA monomer, and after 4 h of reaction. In pursuit of selectively removing metal ions from water, the nanohybrid with the highest grafting (PGE3) was chemically treated with phosphoric acid to introduce phosphonic acid groups on it. FTIR, XRD, SEM, CHO analysis, BET, and TGA analysis were utilized to characterize the developed nanohybrids. Batch adsorption studies were carried out using AAS process, examining the impact of pH, adsorbent weight, contact time, adsorbate concentration, and temperature on the adsorption process. Due to the selectivity of phosphonic acid groups towards copper ions, phosphonic acid-functionalized grafted sepiolite nanohybrid (PGE3-P) was used for copper ions removal from its aqueous solution. The maximum adsorption capacity of PGE3-P adsorbents was 134.5 mg/g for copper ions. The data from kinetic studies suggests that the adsorption process of copper ions followed a pseudosecond-order model. Furthermore, Langmuir isotherm proved to be a more fitting model in equilibrium isothermal investigations. The thermodynamic analysis of the data indicates that the adsorption of copper ions by PGE3-P is an endothermic and spontaneous process. The development of this phosphonic acid-functionalized grafted sepiolite nanohybrid adsorbent is a new contribution into the field of adsorption. The developed material can be utilized as selective adsorbent for elimination of other heavy metals from water.
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Although lithium-ion batteries (LIBs) are extensively used as secondary storage energy devices, they also pose a significant fire and explosion hazard. Subsequently, thermal stability studies for LiPF6- and LiFSI-type electrolytes have been conducted extensively. However, the thermal characteristics of these electrolytes with thermally stable additives in a full cell assembly have yet to be explored. This study presents a comprehensive accelerating rate calorimetry (ARC) study. First, 1.2-Ah cells were prepared using a control commercial LiPF6 electrolyte and LiFSI with a specific succinonitrile additive and ethyl-methyl carbonate as a thermally stable electrolyte additive. The kinetic parameters involved in heat generation and their effects on the thermal properties of the ARC module were analyzed from the heat-wait-seek (HWS), self-heating (SH), and thermal runaway (TR) stages. The results indicate that the addition of a succinonitrile additive to the LiFSI electrolyte lowers the decomposition temperatures of the solid electrolyte interface (SEI) owing to polymerization with Li at the anode, while simultaneously increasing the activation energy of reaction temperatures at SEI between the separator and the electrolyte. The maximum thermal-runaway temperature decreased from 417 °C (ΔH = 5.26 kJ) (LiPF6) to 285 °C (ΔH = 2.068 kJ) (LiFSI + succinonitrile). This study provides key insights to the thermal characteristics of LiPF6 and LiFSI during the self-heating and thermal runaway stages and indicates a practical method for achieving thermally stable LIBs.
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Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC50 values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer.
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The scientific community needs to conduct research on novel electrodes for portable energy storage (PES) devices like supercapacitors (S-Cs) and lithium-ion batteries (Li-ion-Bs) to overcome energy crises, especially in rural areas where no electrical poles are available. Herein, the nanostructured MoS2 and ZnS-MoS2 E-Ms consisting of nanoparticles/rods/sheets (N-Ps-Rs-Ss) are deposited on hierarchical nickel foam by a homemade chemical vapor deposition (H-M CVD) route. The X-ray diffraction patterns confirm the formation of polycrystalline films growing along various orientations, whereas the field-emission scanning electron microscope analysis confirms the formation of N-Ps-Rs-Ss. The change in structural and microstructural parameters indicates the existence of defects improving the energy storage ability of the deposited ZnS-MoS2@Ni-F electrodes. The specific capacitances of MoS2@Ni-F and ZnS-MoS2@Ni-F electrodes are found to be 1763 and 3565 F/g at 0.5 mV/s and 1451 and 3032 F/g at 1 A/g, respectively. The growing behavior of impedance graphs indicates their capacitive nature; however, the shifting of impedance curves toward y-axis indicates that the increasing diffusion rates due to the formation of nanostructures of ZnS-MoS2 results in low impedance. An excellent energy storage performance, minimum capacity fading, and improved electrical conductivity of the deposited E-Ms are due to the combined contributions of the electrical double layer and pseudocapacitor nature, which is again confirmed by theoretical Dunn's model. The absence of charge transfer resistance and good capacitance retention (95%) even after 10,000 cycles indicates that the deposited E-Ms are better for PES devices like S-Cs and Li-ion-Bs than MoS2 E-Ms. The assembled asymmetric supercapacitor device exhibited the maximum specific capacitance = 996 F/g, energy density = 354-285 W h/kg, power density = 2400-24,000 W/kg, capacitance retention = 95% and Coulombic efficiency = 100% even after a long charging-discharging of 10,000 cycles.
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In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5â times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5 b and 5-FU but highlighted stronger interaction of 5 b with EGFR, evident from its lower docking score. Overall, these results signify the notable anti-proliferative potential of most synthesized hybrids, notably emphasizing the efficacy of compound 5 b in suppressing cancer cell growth.
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Antineoplásicos , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Isatina , Simulação de Acoplamento Molecular , Triazóis , Humanos , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Isatina/química , Isatina/farmacologia , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Chalcona/química , Chalcona/farmacologia , Chalcona/síntese química , Estrutura Molecular , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Chalconas/química , Chalconas/farmacologia , Chalconas/síntese química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Covalent organic frameworks (COFs) are promising electrocatalyst platforms owing to their designability, porosity, and stability. Recently, COFs with various chemical structures are developed as efficient electrochemical CO2 reduction catalysts. However, controlling the morphology of COF catalysts remains a challenge, which can limit their electrocatalytic performance. Especially, while porphyrin COFs show promising catalytic properties, their particle size is mostly large and uncontrolled because of the severe aggregation of crystallites. In this work, a new synthetic methodology for rationally downsized COF catalyst particles is reported, where a tritylated amine is employed as a novel protected precursor for COF synthesis. Trityl protection provides high solubility to a porphyrin precursor, while its deprotection proceeds in situ under typical COF synthesis conditions. Subsequent homogeneous nucleation and colloidal growth yield smaller COF particles than a conventional synthesis, owing to suppressed crystallite aggregation. The downsized COF particles exhibit superior catalytic performance in electrochemical CO2 reduction, with higher CO production rate and faradaic efficiency compared to conventional COF particles. The improved performance is attributed to the higher contact area with a conductive agent. This study reveals particle size as an important factor for the evaluation of COF electrocatalysts and provides a strategy to control it.
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We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1 H NMR, 13 C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 µM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c-Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c-Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7-AAD assay indicated apoptosis in MDA-MB-231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA-MB-231 cells than MQ (14.25%). The Caspase 3/7 7-AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ-treated MDA-MB-231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA-MB-231 cells than MQ.