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1.
Drug Dev Ind Pharm ; : 1-13, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39093556

RESUMO

OBJECTIVE: Preparation and characterization of nano-emulsion formulations for Asparagus densiflorus aerial and root parts extracts. SIGNIFICANCE: Genus Asparagus is known for its antimicrobial and anticancer activities, however, freeze dried powder of aqueous - alcoholic extract prepared in this study, exhibited a limited water solubility, limiting its therapeutic application. Thus, encapsulation of its phytochemicals into nano-emulsion is proposed as a solution to improve water solubility, and facilitate its clinical translation. METHODS: the composition of extracts for both aerial and root parts of Asparagus densiflorus was identified by HPLC and LC-MS analysis. Nano-emulsion was prepared via homogenization where a mixture of Castor oil: phosphate buffered saline (10 mM, pH 7.4): Tween 80: PEG 600 in a ratio of 10: 5: 2.5: 2.5, respectively. Nano-emulsion formulations were characterized for particle size, polydispersity index (PDI), zeta potential, TEM, viscosity and pH. Then, the antibacterial and anticancer activities of nano-emulsion formulations versus their pure plant counterparts was assessed. RESULTS: The analysis of extracts identified several flavonoids, phenolics, and saponins which were reported to have antimicrobial and anticancer activities. Nano-emulsion formulations were monodispersed with droplet sizes ranging from 80.27 ± 2.05 to 111.16 ± 1.97 nm, and polydispersity index ≤0.3. Nano-emulsion formulations enhanced significantly the antibacterial (multidrug resistant bacteria causing skin and dental soft tissues infections) and anticancer (HuH7, HEPG2, H460 and HCT116) activities compared to their pure plant extract counterparts. CONCLUSION: Employing a nano-delivery system as a carrier for phytochemicals might be an effective strategy to enhance their pharmacological activity, overcome their limitations, and ultimately increase their potential for clinical applications.

2.
ACS Omega ; 9(30): 32789-32798, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100360

RESUMO

A series of 20 new structure-modified quinolin-2-one derivatives were prepared for biological evaluation. This was successfully achieved based on chemoselective reactions of heterocyclic amides with acrylic acid derivatives, which gave 3-[2-oxoquinolin-1-(2H)-yl] propanoic acid derivatives (N-substitution via a unique behavior). The ester was reacted with hydrazine to afford the corresponding hydrazide. Both the corresponding ester and hydrazide were used as building blocks to modify the quinolone structure and give N-hydroxyl propanamides, oxadiazoles, and thiosemicarbazides. The corresponding carboxylic acid and hydrazide were used to prepare several amides: N-alkyl-3-[2-oxoquinolin-1(2H)-yl]propanamides via azide and dicyclohexyl carbodiimide coupling methods. Among derivatives, compound 9e exhibited potent cytotoxicity against MCF-7 cells with an IC50 value of 1.32 µM compared to doxorubicin with an IC50 value of 1.21 µM. Additionally, it caused potent EGFR inhibition by 97% with an IC50 value of 16.89 nM compared to Erlotinib with an IC50 value of 29.8 nM. Finally, the binding mode of compound interactions toward EGFR was highlighted using a molecular docking study; compound 9e exhibited good binding affinity with a binding energy of -17.89 kcal/mol, and it formed H-bond interactions with Met 769 as the key amino acid of interaction. Accordingly, compound 9e may be developed as an EGFR-oriented chemotherapeutic antibreast cancer agent.

3.
Food Chem ; 461: 140892, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39178540

RESUMO

Carbendazim (CBZ) insecticides have been widely employed, raising serious concerns about their impacts on human health and the environment. A facile hydrothermal technique was used to prepare a zinc ferrite (ZnFe2O4) combined with porous graphene oxide (PGO) as a nanocomposite for selective CBZ detection. The ZnFe2O4/PGO nanocomposite was then used to modify a glassy carbon electrode (GCE), an affordable platform for CBZ detection. Various spectroscopic techniques were employed to confirm the nanomaterial. The electrochemical properties were further investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The ZnFe2O4/PGO nanocomposite modified the glassy carbon electrode surface for CBZ detection. A broad linear response range of 0.0039 to 200 µM, high sensitivity (2.184 µAµM-1 cm-2), a low detection limit of 0.0013 µM, outstanding stability, repeatability, and practical applicability are the intriguing qualities of the ZnFe2O4/PGO-modified electrode for CBZ detection.

4.
Angew Chem Int Ed Engl ; : e202409528, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159334

RESUMO

Vibrational strong coupling can modify chemical reaction pathways in unconventional ways. Thus far, Fabry-Perot cavities formed by pairs of facing mirrors have been mostly utilized to achieve vibrational strong coupling. In this study, we demonstrate the application of non-local metasurfaces that can sustain surface lattice resonances, enabling chemical reactions under vibrational strong coupling. We show that the solvolysis kinetics of para-nitrophenyl acetate can be accelerated by a factor of 2.7 by strong coupling to the carbonyl bond of the solvent and the solute with a surface lattice resonance. Our work introduces a new platform to investigate polaritonic chemical reactions. In contrast to Fabry-Perot cavities, metasurfaces define open optical cavities with single surfaces, which removes alignment hurdles, facilitating polaritonic chemistry across large areas.

5.
Exp Parasitol ; : 108823, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39187057

RESUMO

Trichinosis is a common parasitic disease that affects the striated skeletal muscles, causing apoptotic and degenerative changes associated with myogenin expression in the affected myocytes. Hence, this study aimed to assess the ameliorative effects of stem cells and atorvastatin added to ivermectin on the infected myocytes during the muscular phase of murine trichinosis. 120 laboratory Swiss albino male mice were divided into 10 groups, and each group was subdivided into intestinal and muscular phases (each n = 6); uninfected control; untreated infected control; infected received ivermectin monotherapy; infected received atorvastatin monotherapy; infected received stem cells monotherapy; infected received ivermectin and atorvastatin dual therapy; infected received ivermectin and stem cells dual therapy; infected received atorvastatin and stem cells dual therapy; infected received ivermectin 0.2, atorvastatin 40, and stem cells triple therapy; and infected received ivermectin 0.1, atorvastatin 20, and stem cells triple therapy. Intestinal phase mice were sacrificed on the 5th day post-infection, while those of the muscular phase were sacrificed on the 35th day post-infection. Parasitological, histopathological, ultrastructural, histochemical, biochemical, and myogenin gene expression assessments were performed. The results revealed that mice that received ivermectin, atorvastatin, and stem cell triple therapies showed the maximum reduction in the adult worm and larvae burden, marked improvement in the underlying muscular degenerative changes (as was noticed by histopathological, ultrastructural, and histochemical Feulgen stain assessment), lower biochemical levels of serum NK-κB and tissue NO, and lower myogenin expression. Accordingly, the combination of stem cells, atorvastatin, and ivermectin affords a potential synergistic activity against trichinosis with considerable healing of the underlying degenerative sequel.

6.
Cureus ; 16(7): e65532, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39188479

RESUMO

Background The radial artery originates from the brachial artery at the level of the neck of the radius in the cubital fossa. It has multiple branches all over its course, and it is an important artery for multiple procedures across several fields. Objectives The objective of this article is to assess the size and characteristics of the radial artery in the Saudi population for the transradial approach. It aims to compare the diameters of the distal and proximal radial arteries using ultrasonography and determine the clinical significance of the findings in selecting an appropriate catheter size among different demographic groups. Additionally, the study aims to contrast the obtained results with international standards to provide a comprehensive analysis of the radial artery characteristics in the Saudi population. Methods A pilot study was conducted at a Medina region hospital in Madinah from December 2022 to July 2023. An ultrasonographic assessment of the right radial artery was performed on a sample of 45 volunteers. Results Our results showed a significantly larger mean diameter of the right ulnar artery in males compared to females. No other significant differences were observed in the characteristics of the right proximal radial artery (PRA), distal radial artery (DRA), or ulnar artery between genders. Significant differences in arterial characteristics were observed across different body mass index (BMI) categories for several parameters. Depth measurements in the right PRA displayed notable differences across age groups, and the ulnar artery showed significant variability among age categories. No statistically significant differences were found in arterial characteristics across smoking categories. Conclusion Our study on Saudi Arabian radial artery ultrasonography reveals potential clinical correlations, highlighting the influence of age and BMI on arterial characteristics. Further research is needed to confirm these findings and explore demographic determinants.

7.
RSC Med Chem ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39185453

RESUMO

Chemical investigation of the methanolic extract of Cornulaca monacantha (Amaranthaceae), an annual wild herb collected from North Sinai, Egypt, yielded a new isoflavone cornulacin 1 and five known compounds: N-trans-feruloyltyramine 2, N-trans-feruloyl-3'-methoxytyramine 3, N-trans-caffeoyl tyramine 4, Cannabisin F 5 and (2aS, 3aS) lyciumamide D 6. Using MTT assay, the isolated compounds were evaluated for their in vitro cytotoxicity against pancreatic (Panc1) and ovarian (A2780) cancer cell lines. Compounds 1, 2, 3, and 4 exhibited promising cytotoxic activity against the tested cells, among which compound 1 (IC50 of 2.1 ± 0.21 µM) was the most active one against A2780 cells, whereas compound 2 (IC50 of 3.4 ± 0.11 µM) was the most effective compound against Panc1 cells. Accordingly, compound 1 was further investigated for its apoptotic induction in A2780 cancer cells using Annexin V/PI staining. Compound 1 significantly stimulated apoptotic ovarian A2780 cancer cells by 45.9-fold and arrested cell proliferation in the S-phase. Such activity was mediated through the upregulation of proapoptotic genes Bax; P53; and caspase 3, 8, and 9 besides the downregulation of the Bcl-2 gene, the anti-apoptotic one. Furthermore, molecular docking investigation demonstrated the strong binding affinity of compound 1 with EGFR active sites, which validated its experimental EGFR enzyme inhibition activity.

8.
J Med Chem ; 67(16): 14466-14477, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39088797

RESUMO

Mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that serves a critical function in numerous developmental, morphogenic, and proliferative signaling pathways. If dysregulated, MET has been shown to be involved in the development and survival of several cancers, including non-small cell lung cancer (NSCLC), renal cancer, and other epithelial tumors. Currently, the clinical efficacy of FDA approved MET inhibitors is limited by on-target acquired resistance, dose-limiting toxicities, and less than optimal efficacy against brain metastasis. Therefore, there is still an unmet medical need for the development of MET inhibitors to address these issues. Herein we report the application of structure-based design for the discovery and development of a novel class of brain-penetrant MET inhibitors with enhanced activity against clinically relevant mutations and improved selectivity. Compound 13 with a MET D1228N cell line IC50 value of 23 nM showed good efficacy in an intracranial tumor model and increased the median overall survival of the animals to 100% when dosed orally at 100 mg/kg daily for 21 days.


Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-met , Pirazóis , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Humanos , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Descoberta de Drogas , Pirazinas/farmacologia , Pirazinas/síntese química , Pirazinas/química , Pirazinas/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Camundongos , Mutação , Ratos
9.
Anal Sci ; 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183245

RESUMO

A high-performance liquid chromatographic method (HPLC) with UV detection is described for determination of ceftriaxone sodium (CFX) and cefotaxime sodium (CFM) content in pharmaceutical industrial wastewater. These methods are based on the detection of these antibiotics via the formation of chelate complexes with Cu(II). The developed Liquid Chromatographic method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. The removal percentage reached about 100 and 92.1% at pH 7.2 for CFX and CFM, respectively. In UV detection, the removal of the chelating antibiotics were based on forming of chelate complexes with Cu(II) which detected at λmax = 253 and 244 nm for CFX and CFM, respectively. Linearity, accuracy and precision were found to be acceptable over the concentration range of 5.99-59.86 µg mL-1 for CFX and 14.33-71.63 µg mL-1 for CFM. The proposed method can be used for the quality control of industrial wastewater containing CFX and CFM.

10.
Bioorg Chem ; 151: 107682, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39137597

RESUMO

c-MET and STAT-3 are significant targets for cancer treatments. Here, we describe a class of very effective dual STAT-3 and c-MET inhibitors with coumarin-based thiazoles (3a-o) as its scaffold. Spectroscopic evidence (NMR, HRMS, and HPLC) validated the structural discoveries of the new compounds. The cytotoxic activity of these compounds was also tested against a panel of cancer cells in accordance with US-NCI guidelines. Compound 3g proved to be active at 10 µM, thus it was automatically scheduled to be tested at five doses. Towards SNB-75 (CNS cancer cell line), compound 3g showed notable in vitro anti-cancer activity with GI50 = 1.43 µM. For the molecular targets, compound 3g displayed potent activity towards STAT-3 and c-MET having IC50 of 4.7 µM and 12.67, respectively, compared to Cabozantinib (IC50 = 15 nM of c-MET) and STAT-3-IN-3 (IC50 = 2.1 µM of STAT-3). Moreover, compound 3g significantly induced apoptosis in SNB-75 cells, causing a 3.04-fold increase in apoptotic cell death (treated cells exhibited 11.53 % overall apoptosis, against 3.04 % in reference cells) and a 3.58-fold increase in necrosis. Moreover, it arrests cells at the G2 phase. Dual inhibition of c-MET and STAT-3 protein kinase was further validated using RT-PCR. The target compound's binding mechanism was determined by the application of molecular docking.

11.
Cells ; 13(15)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39120297

RESUMO

Nucleophosmin (NPM1) is a key nucleolar protein released from the nucleolus in response to stress stimuli. NPM1 functions as a stress regulator with nucleic acid and protein chaperone activities, rapidly shuttling between the nucleus and cytoplasm. NPM1 is ubiquitously expressed in tissues and can be found in the nucleolus, nucleoplasm, cytoplasm, and extracellular environment. It plays a central role in various biological processes such as ribosome biogenesis, cell cycle regulation, cell proliferation, DNA damage repair, and apoptosis. In addition, it is highly expressed in cancer cells and solid tumors, and its mutation is a major cause of acute myeloid leukemia (AML). This review focuses on NPM1's structural features, functional diversity, subcellular distribution, and role in stress modulation.


Assuntos
Nucléolo Celular , Proteínas Nucleares , Nucleofosmina , Estresse Fisiológico , Humanos , Proteínas Nucleares/metabolismo , Nucléolo Celular/metabolismo , Animais , Fosfoproteínas/metabolismo
12.
Heliyon ; 10(14): e34418, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39114065

RESUMO

The importance of biomedical physical data is underscored by its crucial role in advancing our comprehension of human health, unraveling the mechanisms underlying diseases, and facilitating the development of innovative medical treatments and interventions. This data serves as a fundamental resource, empowering researchers, healthcare professionals, and scientists to make informed decisions, pioneer research, and ultimately enhance global healthcare quality and individual well-being. It forms a cornerstone in the ongoing pursuit of medical progress and improved healthcare outcomes. This article aims to tackle challenges in estimating unknown parameters and reliability measures related to the modified Weibull distribution when applied to censored progressive biomedical data from the initial failure occurrence. In this context, the article proposes both classical and Bayesian techniques to derive estimates for unknown parameters, survival, and failure rate functions. Bayesian estimates are computed considering both asymmetric and symmetric loss functions. The Markov chain Monte Carlo method is employed to obtain these Bayesian estimates and their corresponding highest posterior density credible intervals. Due to the inherent complexity of these estimators, which cannot be theoretically compared, a simulation study is conducted to evaluate the performance of various estimation procedures. Additionally, a range of optimization criteria is utilized to identify the most effective progressive control strategies. Lastly, the article presents a medical application to illustrate the effectiveness of the proposed estimators. Numerical findings indicate that Bayesian estimates outperform other estimation methods by achieving minimal root mean square errors and narrower interval lengths.

13.
Obes Facts ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116845

RESUMO

INTRODUCTION: This study explores the under-investigated area of obesity-related discrimination and stigmatization across different countries, specifically comparing Spain (Europe) and Egypt (Middle East). METHODS: We conducted a cross-sectional observational study involving 2,090 participants from both countries. Participants completed three well-validated questionnaires to assess their attitudes towards obesity, experiences of weight-related stigma, and internalization of weight bias: Antifat Attitudes Scale (AFA), Stigmatizing Situations Inventory (SSI), and Weight Bias Internalization Scale (WBIS). Participants were categorized into four groups based on BMI and history bariatric surgery. RESULTS: Egyptian participants [BMI = 30.2±6.7 kg/m2 (range: 18.5 to 69.0 kg/m2)] showed significantly higher aversion towards obesity, as indicated by higher AFA score, compared to their Spanish counterparts [BMI = 35.4±10.1 kg/m2 (18.5 to 71,9 kg/m2)]. In contrast, Spanish participants reported higher levels of weight bias internalization with increasing BMI, while in Egypt, this association was negative. The association of bariatric surgery on stigma reduction also differed between the countries. Multivariate analysis revealed that residing in Egypt was an independent risk factor for higher scores in AFA and WBIS (Odds Ratio 8.20 [95% confidence interval: 6.78 to 9.62], p<0.001 and OR 6.28 [95% CI: 4.78 to 7.78], p<0.001; respectively). In contrast, Spaniards experienced more stigmatizing situations than Egyptians [OR -2.54 (95% CI: 6.78 to 9.62), p<0.001]. CONCLUSION: Our study underscore the complex and diverse nature of obesity-related attitudes across cultures. Understanding these cultural differences is crucial for developing effective, culturally sensitive strategies to tackle weight stigma. This research opens avenues for further studies and interventions tailored to cultural contexts.

14.
J Hazard Mater ; 478: 135429, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39128154

RESUMO

Real-time monitoring and tracking of extreme toxins that penetrate into living cells by using biocompatible, low-cost visual detection via fluorescent monitors are vitally essential to reduce health hazards. Herein, we report a simple engineering design of biocompatible and fluorescent sensors/trackers for real-time monitoring and ultra-trace tracking (up to ppb) of extremely toxic substances (such as arsenic species) in living cells. The biocompatible As(V) sensor (BAS) design is fabricated via successful dressing/decoration process of 2-hydroxy 5-methyl isophthalaldehyde fluorescent receptor into hierarchical organic-inorganic carriers that have micro-hollow geodes, swirled caves and nest-shaped cages, and uniform cubic structures. The BAS monitors show evidence for the selective trapping/detecting/tracking of As(V) species in biological cells (i.e., HeLa cells) despite the coexistence of highly competitive and interfered species. Our simple batch-contact sensing assays shows real-space evidence of the continuous monitoring of As(V) species in HeLa cells with ultra-sensitive detection (i.e., with a low detection limit of 0.149 ppb) and rapid recognition (i.e., in the order of seconds). Significantly, the BAS monitors did not affect the cell population and achieved low cytotoxicity and high cell viability during the monitoring/tracking process inside HeLa cells. The high biocompatibility of BAS remarkably allows precise quantification and real-time monitoring/tracking of toxicant targets in living cells.

15.
Cureus ; 16(7): e64238, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39130932

RESUMO

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a rare benign skin tumor originating from hair follicle matrix cells. It typically presents as a firm, painless subcutaneous nodule, most commonly found in the head, neck, and upper extremities. Pilomatrixoma can occasionally appear in atypical locations, posing a diagnostic challenge due to its nonspecific clinical presentation. A 43-year-old female presented with a painless, slowly enlarging mass on the lateral side of her left ankle, which had been present for approximately one year. Physical examination revealed a firm, well-circumscribed subcutaneous nodule measuring about 2 cm in diameter with normal overlying skin. An MRI of the left ankle demonstrated a well-circumscribed, subcutaneous mass with heterogeneous signal intensity, consistent with calcifications, suggesting pilomatrixoma. A fine-needle aspiration biopsy confirmed the presence of basaloid cells, shadow cells, and areas of calcification. The lesion was surgically excised, and histopathological examination validated the diagnosis of pilomatrixoma. The patient had an uneventful postoperative course, with no recurrence at the six-month follow-up. This case underscores the importance of considering pilomatrixoma in the differential diagnosis of subcutaneous nodules, even in unusual locations. A comprehensive diagnostic approach, including clinical evaluation, imaging, and histopathological examination, is essential for an accurate diagnosis. Surgical excision with clear margins is the treatment of choice, ensuring low recurrence rates and excellent patient outcomes. This report enhances the understanding of pilomatrixoma and highlights the necessity for a multimodal diagnostic strategy in managing this rare condition effectively.

16.
RSC Adv ; 14(34): 24992-25006, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39131497

RESUMO

A series of novel piperazine-based bis(thiazoles) 13a-d were synthesized in moderate to good yields via reaction of the bis(thiosemicarbazones) 7a, b with an assortment of C-acetyl-N-aryl-hydrazonoyl chlorides 8a-f. Similar treatment of the bis(thiosemicarbazone) 7a, b with C-aryl-N-phenylhydrazonoyl chlorides 10a, b afforded the expected bis(thiadiazole) based piperazine products 13b-d in reasonable yields. Cyclization of 7a, b with two equivalents of α-haloketones 14a-d led to the production of the corresponding bis(4-arylthiazol)piperazine derivatives 15a-h in good yields. The structures of the synthesized compounds were confirmed from elemental and spectral data (FTIR, MALDI-TOF, 1H, and 13C NMR). The cytotoxicity of the new compounds was screened against hepatoblastoma (HepG2), human colorectal carcinoma (HCT 116), breast cancer (MCF-7), and Human Dermal Fibroblasts (HDF). Interestingly, all compounds showed promising cytotoxicity against most of the cell lines. Interestingly, compounds 7b, 9a, and 9i exhibited IC50 values of 3.5, 12.1, and 1.2 nM, respectively, causing inhibition of 89.7%, 83.7%, and 97.5%, compared to Erlotinib (IC50 = 1.3 nM, 97.8% inhibition). Compound 9i dramatically induced apoptotic cell death by 4.16-fold and necrosis cell death by 4.79-fold. Compound 9i upregulated the apoptosis-related genes and downregulated the Bcl-2 as an anti-apoptotic gene. Accordingly, the most promising EGFR-targeted chemotherapeutic agent to treat colon cancer was found to be compound 9i.

17.
Beilstein J Org Chem ; 20: 1981-1987, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161712

RESUMO

Five new ß-alkylpyrrole derivatives, allostreptopyrroles A-E (1-5), were isolated from the culture broth of Allostreptomyces RD068384. Their structures were elucidated by 1D and 2D NMR spectroscopic analyses, HRESIMS, and chemical derivatization. The absolute configurations of compounds 2 and 3 were predicted by comparison of experimental and calculated specific rotation data. Compounds 1-5 are the first examples of natural pyrroles substituted by formyl and carboxyl functionalities. Compounds 1, 4, and 5 showed cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 µM, respectively, which are less active than the anticancer agent cisplatin, with an IC50 value of 70 µM.

18.
Artigo em Inglês | MEDLINE | ID: mdl-39141582

RESUMO

Heavy metals are crucial carcinogenic agents threatening the environment and living habituates. Among them, arsenic (As) is an important metalloid that is categorized as a group I toxic carcinogen. Roxarsone (RX) is an organoarsenic antibiotic compound primarily used as a veterinarian drug and growth promoter for poultry animals. The extensive usage of RX increased the accumulation of As in living beings and the ecosystem. Therefore, we have prepared an electrochemical sensor based on 3D bismuth oxybromide with 2D selenium-doped graphitic carbon nitride (BOB/SCN) electrocatalyst for the rapid detection of RX. The elemental and structural details were thoroughly investigated with several spectroscopic techniques. The electrochemical properties were measured by impedance and voltammetric measurements. The electrocatalytic behavior toward the RX was estimated with different voltammetric methods. Therefore, our BOB/SCN-based electrochemical sensor demonstrated a low detection limit (2.3 nM), low quantification value (7.7 nM), optimal sensitivity (0.675 µA µM-1 cm-2), and good linear ranges (0.01-77 and 77-857 µM). Additionally, this sensor showed good electrochemical performance and was applied to monitor the RX in various real samples with remarkable recoveries. Based on these results, our BOB/SCN sensor is a promising electrochemical platform for determining RX.

19.
Sci Rep ; 14(1): 19000, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152247

RESUMO

This article presents a compact, wide-angle, polarization-insensitive metamaterial harvester that can efficiently harvest electromagnetic (EM) energy in the S, C, X, and Ku bands. The harvester's unit cell consists of a split ring resonator, two strip lines, and two split strip lines, giving it a total size of (10 × 10) mm2. Each split gap is filled with a 50 Ω resistive load. The input impedance of the harvester is precisely designed to match that of free space, allowing for efficient absorption of EM power and appropriate redirection towards the resistive loads. The harvester's performance is also evaluated for various polarization and incident angles, considering the Transverse Electric and Transverse Magnetic modes. The simulation results reveal that the proposed harvester exhibits a notably greater conversion efficiency of around > 95%. The simulation outcomes were carefully validated through experimental tests conducted in an anechoic chamber using a 3 × 3 cell array of the proposed design. This ensured the accuracy and reliability of the results. The strong correlation between the experimental data and the full-wave simulations strongly supports the effectiveness of the proposed harvester. Therefore, the demonstrated efficiency and compact size make it a perfect fit for energy harvesting systems in wireless sensor networks.

20.
RSC Med Chem ; 15(8): 2937-2958, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39149093

RESUMO

The unique structure of spirooxindoles and their ability to feature various pharmacophoric motifs render them privileged scaffolds for tailoring new multitarget anticancer agents. Herein, a stereoselective multicomponent reaction was utilized to generate a small combinatorial library of pyrazole-tethered spirooxindoles targeting DNA and CDK2 with free radical scavenging potential as an extra bonus. The designed spirooxindoles were directed to combat NSCLC via inducing apoptosis and alleviating oxidative stress. The series' absolute configuration was assigned by X-ray diffraction analysis. Cytotoxicity screening of the developed spirooxindoles against NSCLC A549 and H460 cells compared to normal lung fibroblasts Wi-38 revealed the sensitivity of A549 cells to the compounds and raised 6e and 6h as the study hits (IC50 ∼ 0.09 µM and SI > 3). They damaged DNA at 24.6 and 35.3 nM, and surpassed roscovitine as CDK2 inhibitors (IC50 = 75.6 and 80.2 nM). Docking and MDs simulations postulated their receptors binding modes. The most potent derivative, 6e, induced A549 apoptosis by 40.85% arresting cell cycle at G2/M phase, and exhibited antioxidant activity in a dose-dependent manner compared to Trolox as indicated by DPPH scavenging assay. Finally, in silico ADMET analysis predicted the drug-likeness properties of 6e.

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