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1.
Bioorg Chem ; 142: 106953, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37925887

RESUMO

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.


Assuntos
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-Atividade
2.
Environ Monit Assess ; 196(7): 613, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871952

RESUMO

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.


Assuntos
Biodiversidade , Monitoramento Ambiental , Lagos , Fitoplâncton , Lagos/química , Paquistão , Rios/química , Cianobactérias/crescimento & desenvolvimento , Fósforo/análise , Qualidade da Água
3.
J Public Health (Oxf) ; 45(2): 488-490, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35257179

RESUMO

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.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Estudos Retrospectivos , Hospitais , Medo , Reino Unido/epidemiologia
4.
J Pak Med Assoc ; 73(4): 925-928, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37052018

RESUMO

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.


Assuntos
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 , Abdome
5.
Arch Biochem Biophys ; 732: 109466, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403759

RESUMO

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.


Assuntos
Nanopartículas , Selênio , Humanos , Selênio/uso terapêutico , Inflamação , Microambiente Tumoral , Preparações Farmacêuticas
6.
Molecules ; 27(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164150

RESUMO

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.


Assuntos
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/farmacologia
7.
Aging Male ; 24(1): 92-94, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34319201

RESUMO

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.


Assuntos
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-2
8.
Cell Biol Int ; 44(1): 155-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31393067

RESUMO

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.

9.
Bioorg Med Chem Lett ; 30(22): 127544, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32920143

RESUMO

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.


Assuntos
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/química
10.
J Gene Med ; 17(6-7): 132-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25982931

RESUMO

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.


Assuntos
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 , Transgenes
11.
Virol J ; 11: 117, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24947038

RESUMO

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.


Assuntos
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 Wnt
12.
J Colloid Interface Sci ; 669: 430-443, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38723532

RESUMO

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 âˆ¼ 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 (∼44 µmol g-1 h-1) and ZIS (∼358 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.

13.
Pharmaceutics ; 16(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38399326

RESUMO

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.

14.
ChemMedChem ; : e202400015, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38638026

RESUMO

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 2.5 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.

15.
Heliyon ; 10(9): e29397, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694025

RESUMO

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.

16.
Adv Mater ; 36(19): e2313197, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38300155

RESUMO

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.

17.
Chem Biol Drug Des ; 103(3): e14502, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38453260

RESUMO

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.


Assuntos
Antineoplásicos , Éteres , Humanos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Quinoxalinas/farmacologia , Células HEK293 , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/química , Apoptose , Estrutura Molecular , Relação Estrutura-Atividade
18.
Biol Trace Elem Res ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956009

RESUMO

The increasing levels of heavy metals in aquatic environments, driven by human activities, pose a critical threat to ecosystems' overall health and sustainability. This study investigates the bioaccumulation of heavy metals (Pb, Cu, Cr, and Cd) in water, sediment, and three fish species (Catla catla, Labeo rohita, Cirrhinus mrigala) of different feeding zones within Chashma Barrage, located in the Mianwali district of Punjab, Pakistan, on the Indus River. A comprehensive analysis, including an assessment of associated human health risks, was conducted. Thirty samples from all three sites for each fish species, with an average body weight of 160 ± 32 g, were collected from Chashma Barrage. Water quality parameters indicated suitability for fish growth and health. Heavy metal concentrations were determined using an atomic absorption spectrometer. Results indicated elevated levels of Cd, Cr, and Cu in sediment and Pb and Cd in water, surpassing WHO standard limits. Among the fish species, bottom feeder (C. mrigala) exhibited significantly (P < 0.05) higher heavy metal levels in its tissues (gills, liver, and muscle) compared to column feeder (L. rohita) and surface feeder (C. catla). Liver tissues across all species showed higher heavy metal bioaccumulation, followed by gills. Principal component analysis (PCA) revealed strong correlations among heavy metals in sediment, gills, muscle, and water in every fish species. However, the vector direction suggests that Cr was not correlated with other heavy metals in the system, indicating a different source. The human health risk analysis revealed lower EDI, THQ, and HI values (< 1) for the fish species, indicating no adverse health effects for the exposed population. The study emphasizes the bioaccumulation differences among fish species, underscoring the higher heavy metal concentrations in bottom feeder fish within Chashma Barrage.

19.
Biol Trace Elem Res ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536638

RESUMO

The exposure of fish to heavy metals can significantly impact physiological processes and potentially lead to adverse health effects. This study assesses the effects of exposure to Cd and Pb sublethal concentrations in water on Wallagu attu. A total of 48 fish with an average body weight of 145.5 ± 26 g were distributed among three groups (control, Cd-treated, and Pb-treated) within 60 L fiberglass tanks. They were exposed to 30% sublethal concentrations of Cd and Pb for durations of 1, 15, and 30 days. Following this exposure, an assessment was conducted on metal bioaccumulation and hemato-biochemical responses. Results revealed a significantly (P < 0.05) higher concentration of heavy metals in the fish tissues of metals exposed groups than in the control. The concentration of Cd and Pb increases in fish tissues (kidney > gills > intestine) with exposure time. In most cases, the Pb-exposed group exhibited significantly (P < 0.05) higher concentrations of Pb in different tissues than the Cd-treated group. With extended exposure time, the activities of CAT and SOD show a significant decrease in both Cd and Pb-treated groups. However, the reduction in activities was more pronounced in the Cd-exposed group. On 15 and 30 days, the levels of red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), and total protein (TP) decrease in groups exposed to Cd and Pb. The cortisol and glucose levels exhibit a more noticeable (P < 0.05) increase with prolonged exposure to Cd and Pb than the control group. On day 30, the survival rate decreased more in the Pb-exposed group. The findings of this study indicate that exposure to sublethal doses of Cd and Pb induces stress in Wallagu attu, resulting in rapid changes in specific hemato-biochemical parameters.

20.
Turk J Chem ; 47(6): 1334-1345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38544703

RESUMO

In the present work novel conductive organic-inorganic nanocomposites were produced by grafting of pyrrole monomer onto silanized Laponite RD utilizing emulsion graft polymerization. Influence of some important factors like concentration of monomer, initiator and surfactant were investigated on grafting efficiency. Grafting of polypyrrole chains onto modified Laponite RD was verified by Fourier transform infrared spectroscopy (FT-IR). Scanning electron microscope (SEM) revealed the spherical particles of nanocomposite with average diameter of 271.5 nm. XRD pattern showed that molecular framework of pure polypyrrole almost remains same in nanocomposite. Surface area and pore volume of Laponite RD, measured by Brunauer-Emmett-Teller (BET) analysis, was also altered indicating effective grafting of polypyrrole chains onto modified substrate. Maximum grafting efficiency (%), determined gravimetrically, was 87.3% at monomer, initiator, and surfactant concentrations of 1.50, 1.00, and 0.50% respectively. Prepared nanocomposites with grafting efficiency of 87.3% have displayed maximum electrical conductivity of 0.23 × 10-2 Scm-1. These nanocomposites can be used for manifold applications like biomedical and energy storage devices.

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