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1.
Environ Res ; 250: 118467, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354887

RESUMO

In the aftermath of the Fukushima Daiichi Nuclear Power Plant accident, a pioneering large-scale decontamination project was initiated, aiming to enable the return of evacuees. This project, the first of its kind in human history, involved the transportation of soils collected during decontamination to interim storage facilities. Before recycling or disposal, these soils undergo processes like volume reduction. However, there's a need for innovative methods to reduce volume effectively and treat secondary wastes more efficiently. The current study explores the impact of a dispersant, sodium hexametaphosphate (SHMP), on the behavior of radiocesium (r-Cs: 137Cs) dynamics in different size fractions of radioactively contaminated soils from Fukushima. The solid-phase speciation analysis of Fukushima soils validated that at least 50% of the 137Cs or other minerals are associated with difficult-to-extract soil phases. Nonetheless, the low 137Cs/133Cs ratio in corresponding soil phases implies a slower r-Cs fixation mechanism. The wet-sieving of r-Cs contaminated soil fraction, < 2 mm, with SHMP, resulted in different soil subfractions (2000-212, 212-53, and < 53 µm). Following SHMP treatment, dispersion of > 92% of 137Cs associated with < 212 µm soil size fractions was observed. The migration of 137Cs towards smaller soil size fractions can be attributed to either SHMP-induced cation exchange or the formation of polyvalent complexes involving SHMP and soil minerals. The condensation of 137Cs in < 212 µm, as induced by SHMP, enabled the subsequent reuse of the larger soil fraction (> 212 µm), which was less contaminated. This study provides a new perspective on the effects of dispersants and contributes to a better understanding of the complex interactions among organic carbon, 137Cs, monovalent and polyvalent cations, and soil functional groups concerning the volume reduction of soils contaminated with r-Cs.


Assuntos
Radioisótopos de Césio , Acidente Nuclear de Fukushima , Poluentes Radioativos do Solo , Radioisótopos de Césio/análise , Poluentes Radioativos do Solo/análise , Solo/química , Monitoramento de Radiação/métodos , Descontaminação/métodos , Japão
2.
J Environ Manage ; 346: 118943, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37748284

RESUMO

Ongoing global sustainable development and underground space utilization projects have inadvertently exposed many excavated soils naturally contaminated with geogenic arsenic (As). Recent investigations have revealed that As in certain excavated soils, especially those originating from deep construction projects, has exceeded regulatory limits, threatening the environment and human health. While numerous remediation techniques exist for treating As-contaminated soil, the unique characteristics of geogenic As contamination in excavated soil require specific measures when leachable As content surpasses established regulatory limits. Consequently, several standard leaching tests have been developed globally to assess As leaching from contaminated soil. However, a comprehensive comparative analysis of these methods and their implementation in contaminated excavated soils remains lacking. Furthermore, the suitability and efficacy of most conventional and advanced techniques for remediating As-contaminated excavated soils remained unexplored. Therefore, this study critically reviews relevant literature and summarize recent research findings concerning the management and mitigation of geogenic As in naturally contaminated excavated soil. The objective of this study was to outline present status of excavated soil globally, the extent and mode of As enrichment, management and mitigation approaches for As-contaminated soil, global excavated soil recycling strategies, and relevant soil contamination countermeasure laws. Additionally, the study provides a concise overview and comparison of standard As leaching tests developed across different countries. Furthermore, this review assessed the suitability of prominent and widely accepted As remediation techniques based on their applicability, acceptability, cost-effectiveness, duration, and overall treatment efficiency. This comprehensive review contributes to a more profound comprehension of the challenges linked to geogenic As contamination in excavated soils.

3.
Bioorg Chem ; 127: 105964, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35759881

RESUMO

Multitargeting kinase inhibitors recently proved to be a profitable approach for conquering cancer proliferation. The current study represents the design and synthesis of new thiophene, thienopyridine, and thiazoline-based derivatives 4-14a,b. All the target compounds were examined in vitro against three cancer cell lines; the liver (HepG-2), breast (MCF-7), and colon (HCT-116) where the thiophene-based compounds 5a-c, demonstrated the most potent activity. Furthermore, the latter derivatives revealed a safety profile against WI-38 normal cell line of selectivity indices ranging from 4.43 to 17.44. In vitro enzyme assay of 5a-c revealed that the carbohydrazide analog 5c has the most promising multitargeting inhibiting activity against Pim-1, VEGFR-2, and EGFRWT enzymes of IC50 values; 0.037 ± 0.02, 0.95 ± 0.24, and 0.16 ± 0.05 µM, respectively. As it was the most potent analog, 5c was further subjected to cell cycle and apoptosis analysis. The results indicated that it induced preG1 arrest and an apoptotic effect in the early and late stages. Moreover, further apoptosis studies were carried out for 5c to evaluate its proapoptotic potential. Interestingly, 5c enhanced the levels of Bax/Bcl-2 ratio, p53, and active caspase 3 by 18, 6.4, and 24 folds, respectively compared to the untreated cells. The antimicrobial evaluation showed that only compounds 3 and 5a produced broad-spectrum potency, while 5b and 5c exhibited outstanding antifungal effects. Finally, a molecular docking study was carried out to discover the probable interactions of compound 5c with the active sites of Pim-1, VEGFR-2, and EGFRWT kinases.


Assuntos
Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases , Relação Estrutura-Atividade , Tienopiridinas/farmacologia , Tiofenos/química
4.
Appl Opt ; 61(15): 4535-4542, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36256295

RESUMO

Perovskite solar cells (PSCs) have shown a significant improvement in cell performance in photovoltaics technology. The commonly used light absorbing material of halide-based perovskite in PSCs has produced high efficiency cells with low cost and a simple fabrication process. However, it contains the harmful substance of Pb, which affects the environment, and the cell still suffers from instability in the long run. Therefore, this work presents a theoretical study of the Pb-free absorber layer of CH3NH3SnI3 that is paired for compatibility with various types of hole transport layers (HTLs). Several key parameters of the absorbent layer and HTL have been optimized to produce the highest power conversion efficiency (PCE) using 1D-SCAPS software under AM 1.5 illumination. It was found that the combination of Cu2O and CH3NH3SnI3 used as the HTL and absorbent layer, respectively, has resulted in great PCE as high as 27.72%. These findings prove that the use of inorganic HTLs and Pb-free perovskite layers is promising for use in PSCs.

5.
Lett Appl Microbiol ; 75(3): 511-525, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35485872

RESUMO

Marine micro-organisms are a promising source for novel natural compounds with many medical and biotechnological applications. Here, we demonstrate limitations and recent strategies for investigating the marine microbial community for novel bioactive metabolites, specifically those of antimicrobial potential. These strategies include culture-dependent methods such as modifying the standard culture media, including changing the gelling agent, dissolving vehicle, media supplementation and preparation to access a broader range of bacterial diversity from marine samples. Furthermore, we discuss strategies such as in situ cultivation, dilution-to-extinction cultivation and long-term incubation. We are presenting recent applications of culture-independent methods such as genome mining, proteomics profiling and the application of metagenomics as a novel strategy for structure confirmation in the discovery of the marine micro-organism for novel antimicrobial metabolites. We present this review as a simple guide and a helpful resource for those who seek to enter the challenging field of applied marine microbiology.


Assuntos
Anti-Infecciosos , Produtos Biológicos , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Anti-Infecciosos/química , Organismos Aquáticos , Bactérias/metabolismo , Produtos Biológicos/farmacologia , Meios de Cultura/metabolismo , Metagenômica
6.
Bioorg Chem ; 109: 104704, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33609915

RESUMO

New substituted pyrazolone and dipyrazolotriazine derivatives have been synthesized, designed and well characterized as promising dual antimicrobial/antioxidant agents to overcome multidrug resistant bacteria (MDR), oxidative stress and their related diseases. Among all strains, S. aureus was found to be the most susceptible for all compounds except 10b and 12b. Out of the three investigated series, sulfonamide analogues 5a-c displayed excellent antibacterial activity with 5b (MIC = 7.61 µM) and 5a (MIC = 8.98 µM) displaying activity that exceeds the reference drug tetracycline (MIC = 11.77 µM). The same sulfonamide derivatives 5a-c demonstrates high ABTS scavenging capacity comparable to standard. Moreover, the structure-activity relationship (SAR) revealed that benzenesulfonamide is a crucial group for enhancing activity. Molecular docking studies of the potent analogues were performed by targeting the crystal structures of S. aureus tyrosyl-tRNA synthetase and human peroxiredoxin-5 enzymes and the obtained results supported well the in vitro data revealing stronger binding interactions. Pharmacokinetics prediction together with modeling outcomes suggests that our sulfonamide derivatives may serve as useful lead compounds for the treatment of infectious disease.


Assuntos
Simulação de Acoplamento Molecular , Peroxirredoxinas/antagonistas & inibidores , Pirazolonas/química , Pirazolonas/farmacologia , Triazinas/farmacologia , Tirosina-tRNA Ligase/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Modelos Moleculares , Estrutura Molecular , Staphylococcus aureus/enzimologia , Relação Estrutura-Atividade , Triazinas/química
7.
Bioorg Chem ; 114: 105078, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34161878

RESUMO

This study was focused on the synthesis of new pyrimidines 4a,b, 5a,b and pyrazoles 6a, b as ATP mimicking tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR). The new compounds were assessed as cytotoxic candidates against human breast cancer cells (MCF-7) and hepatocellular carcinoma cells (HepG-2). All the new compounds appeared as more potent cytotoxic agents than erlotinib, while only compound 4a exhibited more potency than 5-flourouracil and 4b analogue was equipotent to it. Accordingly, the kinase suppression effect of 4a and 4b was further evaluated against EGFRWT, EGFRL858R and EGFRT790M. Both pyrimidine analogues 4a and 4b displayed outstanding inhibitory activity against EGFRWT and its two mutated isoforms EGFRL858R and EGFRT790M in comparing to erlotinib and osimertinib as reference drugs. Additionally, all the new analogues were subjected to antimicrobial assay. Interestingly, both 4a and 4b represented the most promising activity of wide spectrum antimicrobial effect against the examined microbes in comparison to gentamycin and ketoconazole as standard drugs. Moreover, docking results proved the good binding interactions of the compounds 4a and 4b with EGFRWT and EGFRT790M which were in accordance with the results of the in vitro enzyme assay. Additional in silico ADMET studies were performed for the new derivatives which represented their good oral absorption, good drug-likeness properties and low toxicity risks in human.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Aspergillus fumigatus/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Mucorales/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteus vulgaris/efeitos dos fármacos , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Streptococcus/efeitos dos fármacos , Relação Estrutura-Atividade
8.
Bioorg Chem ; 102: 104105, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717689

RESUMO

In our effort of discovering new antimicrobial agents, a novel series of imidazo[4,5-b]pyridine-5-thione scaffolds were designed and synthesized and their chemical structures were characterized by physicochemical and spectral analysis. The synthesized compounds were assessed for their in vitro antimicrobial activities against pathogenic microorganisms. Results revealed that out the tested compounds, 3 exhibited the potent inhibitory effect (MIC = 0.49 µg/mL) as compared to the positive control, chloramphenicol (0.98 µg/mL) which predicted also to have the best pharmacokinetic and druglikness properties as well as lower toxicity profiles. Preliminary structure-activity relationships (SARs) study has been also investigated. Moreover, to understand the binding patterns of the tested compounds in the Staphylococcus aureus tyrosyl-tRNA synthetase active site, molecular docking study using the most active compound 3 was carried out. The obtained results indicate that analog 3 can potentially bound to the target enzyme with the highest docking score (-9.37 kcal/mol). Overall, our results showed that antimicrobial activity as well as ADMET and toxicity predictions were in consensus with the docking results.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Staphylococcus aureus/enzimologia , Tirosina-tRNA Ligase/antagonistas & inibidores , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Aspergillus/efeitos dos fármacos , Bacillus cereus/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Imidazóis/síntese química , Imidazóis/química , Imidazóis/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Piridinas/farmacologia , Relação Estrutura-Atividade , Tionas/síntese química , Tionas/química , Tionas/farmacologia , Tirosina-tRNA Ligase/metabolismo
9.
J Enzyme Inhib Med Chem ; 35(1): 1491-1502, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32668994

RESUMO

A novel series of pyrazole analogues including hydrazones, pyrazolo[4,3-c]-pyridazines, pyrazolo[3,4-e][1,2,4]triazine and pyrazolo[3,4-d][1,2,3]triazoles was designed, synthesised and screened for their in vitro antimicrobial and DHFR inhibition activity. Compounds bearing benzenesulphonamide moiety incorporated with 3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene) hydrazine 3a or 6-amino-7-cyano-3-methyl-5H-pyrazolo[4,3-c]pyridazine 6a revealed excellent and broad spectrum antimicrobial activity comparable to ciprofloxacin and amphotericin B as positive antibiotic and antifungal controls, respectively. Furthermore, these derivatives proved to be the most active DHFR inhibitors with IC50 values 0.11 ± 1.05 and 0.09 ± 0.91 µM, in comparison with methotrexate (IC50 = 0.14 ± 1.25 µM). The in silico studies were done to calculate the drug-likeness and toxicity risk parameters of the newly synthesised derivatives. Additionally, the high potency of the pyrazole derivatives bearing sulphonamide against DHFR was confirmed with molecular docking and might be used as an optimum lead for further modification.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Compostos Heterocíclicos/farmacologia , Pirazóis/farmacologia , Tetra-Hidrofolato Desidrogenase/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Aspergillus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Antagonistas do Ácido Fólico/síntese química , Antagonistas do Ácido Fólico/química , Compostos Heterocíclicos/química , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Pirazóis/química , Streptococcus pneumoniae/efeitos dos fármacos , Relação Estrutura-Atividade
10.
J Environ Manage ; 259: 110018, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32072959

RESUMO

In the study, the dynamics of Sr2+ and geochemically correlated elements (Ca2+, Ba2+, and Y3+) in soil with chelators in the mix (soil to chelator ratio, 1:10; matrix, H2O) were assessed to understand chemical-induced washing remediation of radiogenic waste solids. Specifically, EDTA (2,2',2″,2‴-(ethane-1,2-diyldinitrilo)tetraacetic acid), EDDS (2-[2-(1,2-dicarboxyethylamino)ethylamino]butanedioic acid), GLDA (2-[bis(carboxymethyl)amino]pentanedioic acid), and HIDS (2-(1,2-dicarboxyethylamino)-3-hydroxy-butanedioic acid) are chelators that are used as extractants. The effect of solution pH on chelator-induced extractions of the target elements (t-Es: Sr2+, Ca2+, Ba2+, or Y3+) from soil and stability constants of the t-Es complexes with chelators were used to explain the trends and magnitudes in interactions. Pre- and post-extractive solid-phase speciation was used to define the extent of the competence of each chelator in persuading dissolution of t-Es in the soil. The effects of ultrasonic energy, admixtures of biodegradable chelators, and excess chelators in solution (1:20) were also analyzed on the extractive removal of t-Es from soil. The results indicate that the Sr2+ removal with biodegradable chelators significantly exceeded (approximately 70%) when compared to that of environmentally-persistent EDTA at lower solution pHs and a higher soil to chelator ratio (GLDA > HIDS > EDDS ≈ EDTA). However, the extraction of the geochemically related element was significantly lower.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Quelantes , Ácido Edético , Solo , Estrôncio
11.
J Enzyme Inhib Med Chem ; 34(1): 1259-1270, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31287341

RESUMO

Pyrazolylphthalimide derivative 4 was synthesized and reacted with different reagents to afford the target compounds imidazopyrazoles 5-7, pyrazolopyrimidines 9, 12, 14 and pyrazolotriazines 16, 17 containing phthalimide moiety. The prepared compounds were established by different spectral data and elemental analyses. Additionally, all synthesized derivatives were screened for their antibacterial activity against four types of Gram + ve and Gram-ve strains, and for antifungal activity against two fungi micro-organisms by well diffusion method. Moreover, the antiproliferative activity was tested for all compounds against human liver (HepG-2) cell line in comparison with the reference vinblastine. Moreover, drug-likeness and toxicity risk parameters of the newly synthesized compounds were calculated using in silico studies. The data from structure-actvity relationship (SAR) analysis suggested that phthalimide derivative bearing 3-aminopyrazolone moiety, 4 illustrated the best antimicrobial and antitumor activities and might be considered as a lead for further optimization. To investigate the mechanism of the antimicrobial and anticancer activities, enzymatic assay and molecular docking studies were carried out on E. coli topoisomerase II DNA gyrase B and VEGFR-2 enzymes.


Assuntos
Ftalimidas/química , Ftalimidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ftalimidas/síntese química , Análise Espectral/métodos , Relação Estrutura-Atividade
12.
J Environ Manage ; 240: 374-383, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30953991

RESUMO

In Bangladesh, India, and Pakistan the ship breaking (SB) sector dismantles end-of-life ships on open beaches, exposing the environment to the resulting pollution, especially the soil and water. Because SB occurs in the vicinity of other poorly-regulated activities in industrial zones (IZ) in these countries, there is some ambiguity concerning the relative roles played by SB and IZ in the accumulation of hazardous materials in the soil. In the absence of comparative studies, this study investigated the relative levels of soil contamination due to SB or IZ in the same geographic region by taking soil samples from SB and unrelated IZs in Chittagong, Bangladesh. The technogenic input of sixty-four chemical elements into the soil at the SB or IZ were compared with off-site reference values or the natural content of these elements in the Earth's crust and surface. The magnitude of soil contamination by ecotoxic elements, the corresponding bioavailability, and the ecological risks were assessed based on the regulatory reference values (RRVs) and with other approaches using data aggregation. Among the different potentially toxic elements, Cr, Cu, Ni, Pb, and Zn were found to be above the maximum allowable concentration (p < 0.05) in both SB and IZ. Moderate-to-high soil contamination from SB and moderate-to-considerable soil contamination in the IZ were observed. However, the element-bioavailability as ascertained via solid-phase speciation or weak-acid induced leaching, and the evaluation of associated ecological risk both indicated a low hazard quotient for soils from both SB and IZ. The outcome of the current research marked both SB and IZ soils as contaminated but not polluted, yet remediation is suggested. The level of contamination in SB soils was relatively higher than that of IZ. The comparative results presented in this study for the first time will hopefully be useful as a reference for future ecological and geochemical studies concerning the environmental contamination associated with both ship recycling on open beaches and other typical industrial activities.


Assuntos
Metais Pesados , Poluentes do Solo , Bangladesh , Monitoramento Ambiental , Índia , Paquistão , Medição de Risco , Navios , Solo
13.
Sci Rep ; 14(1): 7993, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580708

RESUMO

The current work aimed to improve the combustion behavior of a non-premixed twin-jet inlet. The effect of fuel and air inlet shape under different velocities was studied using ANSYS as the process takes place in species transport and finite rate/eddy dissipation, and the flow is considered to be turbulent. Two different shapes (circular-circular and circular-elliptic inlet jets) were investigated, and the results show that the behavior and intensity of the fire are affected by variations in the speed and, geometry of the inlet which affects temperature, heat release rate, combustion efficiency, and equivalent ratios. The optimum air/fuel velocities were found to be 2.5/1.5 with circular-circular inlet jets.

14.
Environ Sci Pollut Res Int ; 30(19): 54470-54482, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36995503

RESUMO

Potentially toxic elements (PTEs) in soils accumulate in plants, obstruct their growth, and pose hazards to the consumer via the food chain. Many kinds of grass, grass-like plants, and other higher plant species have evolved a tolerance to PTEs. Holcus lanatus L., a wild grass, is also tolerant (an excluder) of PTEs, such as arsenic (As), cadmium (Cd), lead (Pb), and zinc (Zn). However, the extent of tolerance varies among ecotypes and genotypes. The PTE tolerance mechanism of H. lanatus curtails the typical uptake process and causes a reduced translocation of PTEs from the roots to the shoots, while such a characteristic is useful for contaminated land management. The ecology and response patterns of Holcus lanatus L. to PTEs, along with the associated mechanisms, are reviewed in the current work.


Assuntos
Arsênio , Holcus , Metais Pesados , Poluentes do Solo , Poaceae , Solo , Arsênio/análise , Raízes de Plantas/química , Poluentes do Solo/análise
15.
RSC Adv ; 13(19): 12889-12905, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37114032

RESUMO

c-Met tyrosine kinase plays a key role in the oncogenic process. Inhibition of the c-Met has emerged as an attractive target for human cancer treatment. This work deals with the design and synthesis of a new set of derivatives bearing pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b]thieno[3,2-e]pyridine, and pyrazolo[3,4-d]thiazole-5-thione scaffolds, 5a,b, 8a-f, and 10a,b, respectively, utilizing 3-methyl-1-tosyl-1H-pyrazol-5(4H)-one (1) as a key starting material. All the new compounds were evaluated as antiproliferative agents against HepG-2, MCF-7, and HCT-116 human cancer cell lines utilizing 5-fluorouracil and erlotinib as two standard drugs. Compounds 5a,b and 10a,b represented the most promising cytotoxic activity of IC50 values ranging from 3.42 ± 1.31 to 17.16 ± 0.37 µM. Both 5a and 5b showed the most cytotoxicity and selectivity toward HepG-2, with IC50 values of 3.42 ± 1.31 µM and 3.56 ± 1.5 µM, respectively. The enzyme assay demonstrated that 5a and 5b had inhibition potency on c-Met with IC50 values in nanomolar range of 4.27 ± 0.31 and 7.95 ± 0.17 nM, respectively in comparison with the reference drug cabozantinib (IC50; 5.38 ± 0.35 nM). The impact of 5a on the cell cycle and apoptosis induction potential in HepG-2 and on the apoptotic parameters; Bax, Bcl-2, p53, and caspase-3 was also investigated. Finally, the molecular docking simulation of the most promising derivatives 5a and 5b was screened against c-Met to investigate the binding patterns of both compounds in the active site of the c-Met enzyme. In silico ADME studies were also performed for 5a and 5b to predict their physicochemical and pharmacokinetic characteristics.

16.
Environ Sci Pollut Res Int ; 30(43): 98246-98260, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37606771

RESUMO

The growth response and incorporation of As into the Sargassum horneri was evaluated for up to 7 days using either arsenate (As(V)), arsenite (As(III)) or methylarsonate (MMAA(V) and DMAA(V)) at 0, 0.25, 0.5, 1, 2, and 4 µM with various phosphate (P) levels (0, 2.5, 5 and 10 µM). Except As(III), algal chlorophyll fluorescence was almost similar and insignificant, regardless of whether different concentrations of P or As(V) or MMAA(V) or DMAA(V) were provided (p > 0.05). As(III) at higher concentrations negatively affected algal growth rate, though concentrations of all As species had significant effects on growth rate (p < 0.01). Growth studies indicated that toxicity and sensitivity of As species to the algae followed the trend: As(III) > As(V) > MMAA(V) ~ DMAA(V). As bioaccumulation was varied significantly depending on the increasing concentrations of all As species and increasing P levels considerably affected As(V) uptake but no other As species uptake (p < 0.01). The algae accumulated As(V) and As(III) more efficiently than MMAA(V) and DMAA(V). At equal concentrations of As (4 µM) and P (0 µM), the alga was able to accumulate 638.2 ± 71.3, 404.1 ± 70.6, 176.7 ± 19.6, and 205.6 ± 33.2 nM g-1 dry weight of As from As(V), As(III), MMAA(V), and DMAA(V), respectively. The influence of low P levels with increased As(V) concentrations more steeply increased As uptake, but P on other As species did not display similar trends. The algae also showed passive modes for As adsorption of all As species. The maximum adsorption of As (63.7 ± 6.1 nM g-1 dry weight) was found due to 4 µM As(V) exposure, which was 2.5, 7.3, and 6.9 times higher than the adsorption amounts for the same concentration of As(III), MMAA(V), and DMAA(V) exposure, respectively. The bioavailability and accumulation behaviors of As were significantly influenced by P and As species, and this information is essential for As research on marine ecosystems.


Assuntos
Arsênio , Sargassum , Bioacumulação , Disponibilidade Biológica , Ecossistema , Fosfatos
17.
Artigo em Inglês | MEDLINE | ID: mdl-37171725

RESUMO

The current study sought to determine the levels of radioactivity and heavy metal contamination in 22 dried fish samples collected in Chennai, Tamil Nadu. The study found that there were substantial heavy metals concentrations for Pb, Mn, Cr, Co, and Cd. The concentration of heavy metal Pb being alarmingly high (32.85 to 42.09 mg/kg), followed by Cd (2.18 mg/kg to 3.51 mg/kg) than the permissible limit of WHO (2.17 mg/kg) for Pb and (0.05 mg/kg) for Cd. In terms of radioactivity, the gross alpha activity in the dried fish samples ranged 6.25 ± 0.12 to 48.21 ± 0.11 Bg/kg with an average of 20.35 Bg/kg and with a gross beta activity from 6.48 ± 0.02 to 479.47 ± 0.65 Bg/kg, for an average of 136.83 Bg/kg. The study found that the internal radiation dose that people receive upon consuming the fish species Sphyraena obtusata, Rachycentron canadum, Lepidocephalichthys thermalis, Synodontidae, Carangoides malabaricus, Sardina pilchardus, Scomberomorus commerson, Sillago sihama, Gerres subfasciatus, and Amblypharyngodon mola is above the ICRP-recommended limit of less than 1 mSv/year. Annual gonadal dose equivalent (AGDE) and total excessive lifetime cancer risk (ELCR) ranged 0.488 µSv year-1 and 0.004 µSv year-1 respectively, the values of AGDE being higher than the global average value. The findings of the study indicate that the analyzed dried fish samples are contaminated with Pb and Cd, which shall pose cancer risk to the consumers as a result.

18.
Environ Sci Pollut Res Int ; 30(52): 112052-112070, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37824052

RESUMO

Excavated debris (soil and rock) contaminated with geogenic arsenic (As) is an increasing concern for regulatory organizations and construction stakeholders. Chelator-assisted soil flushing is a promising method for practical on-site remediation of As-contaminated soil, offering technical, economic, and environmental benefits. Ethylenediaminetetraacetic acid (EDTA) is the most prevalent chelator used for remediating As-contaminated soil. However, the extensive environmental persistence and potential toxicity of EDTA necessitate the exploration of eco-compliant alternatives. In this study, the feasibility of the conventional flushing method pump-and-treat and two newly designed immersion and sprinkling techniques were evaluated at the laboratory scale (small-scale laboratory experiments) for the on-site treatment of As-contaminated excavated debris. Two biodegradable chelators, L-glutamic acid-N,N'-diacetic acid (GLDA) and 3-hydroxy-2,2'-iminodisuccinic acid (HIDS), were examined as eco-friendly substitutes for EDTA. Additionally, this study highlights a useful post-treatment measure to ensure minimal mobility of residual As in the chelator-treated debris residues. The pump-and-treat method displayed rapid As-remediation (t, 3 h), but it required a substantial volume of washing solution (100 mL g-1). Conversely, the immersion technique demonstrated an excellent As-extraction rate using a relatively smaller washing solution (0.33 mL g-1) and shorter immersion time (t, 3 h). In contrast, the sprinkling technique showed an increased As-extraction rate over an extended period (t, 48 h). Among the chelators employed, the biodegradable chelator HIDS (10 mmol L-1; pH, 3) exhibited the highest As-extraction efficiency. Furthermore, the post-treatment of chelator-treated debris with FeCl3 and CaO successfully reduced the leachable As content below the permissible limit.


Assuntos
Arsênio , Recuperação e Remediação Ambiental , Isópodes , Poluentes do Solo , Animais , Arsênio/análise , Ácido Edético/química , Poluentes do Solo/análise , Quelantes/química , Solo/química
19.
Thorac Cardiovasc Surg ; 60(1): 35-42, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21528470

RESUMO

BACKGROUND: Our purpose was to evaluate and compare the accuracy of the "Sequential Organ Failure Assessment" score (SOFA) and the "Cardiac Surgery Score" (CASUS) for the prediction of mortality after cardiac surgery. METHODS: Between January 1, 2007 and December 31, 2008 we prospectively included all consecutive adult patients admitted to our intensive care unit (ICU) after cardiac surgery. Both scoring systems were calculated daily from the 1st day in the ICU (day of operation) until the 7th ICU day. We evaluated the ICU mortality prediction of both models using calibration and discrimination statistics. RESULTS: 2801 patients (29.6% females) were included. Mean age was 66.9 ± 10.7 years. Intensive care unit mortality was 5.2%. The calibration of the "Sequential Organ Failure Assessment Score" and "Cardiac Surgery Score" was reliable for all days (p ≥ 0.05). CASUS was more accurate in predicting survival and mortality compared to SOFA for all days, as evidenced by the larger areas under the Receiver Operating Characteristic curves. CONCLUSIONS: Both CASUS and SOFA are reliable mortality prediction tools after cardiac surgery. However, CASUS was more accurate in predicting the individual patient's risk of mortality. Thus, use of the CASUS in cardiac surgery intensive care units is recommended.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Indicadores Básicos de Saúde , Insuficiência de Múltiplos Órgãos/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Distribuição de Qui-Quadrado , Análise Discriminante , Feminino , Alemanha , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Prospectivos , Curva ROC , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
East Mediterr Health J ; 18(10): 1065-71, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23301363

RESUMO

This study examined haematopoietic stem cells of 19 high-risk cases of myelodysplastic syndrome (MDS) for apoptotic and anti-apoptotic signals and cellular proliferation and correlated these with clinical and cytogenetic subtypes, particularly trisomy 8. The aim was to identify cellular and cytogenetic markers of prognostic relevance to survival of high-risk MDS cases. High-risk MDS cases had a significantly higher percentage of apoptotic CD34+ cells and anti-apoptotic survivin+ cells than controls, particularly for trisomy 8 cases. Trisomy 8+ cells showed a significant positive correlation with apoptotic CD34+ cells and capacity for colony formation. The latter was significantly lower in trisomy-8-negative cases than normal controls, while that oftrisomy 8 cases was comparable to controls. Our results suggest that although trisomy 8 cells are in a pro-apoptotic state, they are checked by the enhanced expression of anti-apoptotic signals which provide them with their proliferative advantage.


Assuntos
Antígenos CD34/imunologia , Células-Tronco Hematopoéticas/imunologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/imunologia , Trissomia/genética , Apoptose/imunologia , Proliferação de Células , Cromossomos Humanos Par 8/genética , Humanos , Fatores de Risco
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