EGFR and PI3K/m-TOR inhibitors: design, microwave assisted synthesis and anticancer activity of thiazole–coumarin hybridsBatran, Rasha Z.; Ahmed, Eman Y.; Awad, Hanem M.; Ali, Korany A.; Latif, Nehad A. Abdel
doi: 10.1039/d3ra03483fpmid: 37800132
A series of thiazoline and thiazolidinone-based 4-hydroxycoumarin derivatives were synthesized using both conventional synthesis procedures and microwave-assisted techniques. The new compounds were evaluated for their cytotoxic effect against three human cancer cell lines; MCF-7, HCT-116 and HepG2 and one normal human cell line (BJ-1). The promising anti-proliferative compounds 2a, 2b, 6a and 6b were assessed for inhibiting EGFR and PI3K/mTOR. Compound 6a showed the highest inhibition activity towards the signaling pathway. The apoptotic effect and cell cycle arrest potential of derivative 6a were examined. Moreover, the molecular docking, physicochemical properties and pharmacokinetic parameters of the promising compound were investigated, as well.
Polyethyleneimine-assisted formation of Ag–SiO2 hybrid microspheres for H2O2 sensing and SERS applicationsMehta, Swati; Bahadur, Jitendra; Sen, Debasis; Nechiyil, Divya; Bhatt, H.; Kumar, Naveen; Prakash, Jyoti
doi: 10.1039/d3ra04095jpmid: 37800133
Herein, we report a simple, cost-effective, and eco-friendly approach for producing polyethyleneimine (PEI)-assisted silver nanoparticle-supported silica microspheres through evaporation-induced assembly (EIA). The silica–PEI microspheres obtained through EIA consisted of highly trapped PEI molecules owing to their electrosorption onto oppositely charged silica colloids. The trapped PEI molecules in the microspheres played a crucial role in linking silver ions to form silver ion–PEI complexes, which were then reduced to form silver nanoparticles. Further, the complex interactions between PEI and silica colloids led to enhanced porosity in the microspheres, enabling the efficient adsorption of Ag ions. The characterization of the Ag–SiO2 microspheres was carried out using various techniques, including field-emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), small-angle X-ray scattering (SAXS), and Fourier transform infrared (FTIR) spectroscopy, which confirmed the successful formation of Ag nanoparticles on microspheres, and a plausible formation mechanism is elucidated. The Ag–SiO2 microspheres exhibited good sensing properties for hydrogen peroxide (H2O2), with an estimated limit of detection of 1.08 mM and a sensitivity of 0.033 μA mM−1 mm−2. The microspheres were also used as a surface-enhanced Raman scattering (SERS) substrate, which demonstrated high sensitivity in detecting rhodamine 6G down to a concentration of 2 × 10−6 M. The present approach elucidates a promising alternative to conventional methods that face challenges, such as scalability issues, complex and cumbersome synthesis procedures, and the use of strong reducing agents. With the potential for industrial-level scalability, this method offers a viable strategy for producing Ag–SiO2 microspheres with possible applications in biomedical and sensing technologies.
Copper-mediated synthesis of temperature-responsive poly(N-acryloyl glycinamide) polymers: a step towards greener and simple polymerisationKřivánková, Nikola; Kaya, Kerem; van der Wijngaart, Wouter; Edlund, Ulrica
doi: 10.1039/d3ra04993kpmid: 37800134
Stimuli-responsive materials with reversible supramolecular networks controlled by a change in temperature are of interest in medicine, biomedicine and analytical chemistry. For these materials to become more impactful, the development of greener synthetic practices with more sustainable solvents, lower energy consumption and a reduction in metallic catalysts is needed. In this work, we investigate the polymerisation of N-acryloyl glycinamide monomer by single-electron transfer reversible-deactivation radical polymerisation and its effect on the cloud point of the resulting PNAGA polymers. We accomplished 80% conversion within 5 min in water media using a copper wire catalyst. The material exhibited a sharp upper critical solution temperature (UCST) phase transition (10–80% transition within 6 K). These results indicate that UCST-exhibiting PNAGA can be synthesized at ambient temperatures and under non-inert conditions, eliminating the cost- and energy-consuming deoxygenation step. The choice of copper wire as the catalyst allows the possibility of catalyst recycling. Furthermore, we show that the reaction is feasible in a simple vial which would facilitate upscaling.
Optimized synthesis of polyacrylic acid-coated magnetic nanoparticles for high-efficiency DNA isolation and size selectionBali, Nesrine; Brennhaug, Svein J.; Bjørås, Magnar; Bandyopadhyay, Sulalit; Manaf, Adeel
doi: 10.1039/d3ra04687gpmid: 37800135
Solid-phase reversible immobilization (SPRI) bead technology is widely used in molecular biology for convenient DNA manipulation. However, commercial SPRI bead kits lack cost advantages and flexibility. It is, therefore, necessary to develop new and alternative cost-effective methods of on-par or better quality. Herein, an easy and cost-effective method is proposed for synthesizing polyacrylic acid-coated iron oxide nanoparticles (PAA-IONPs) through in situ polymerization at lab scale for high-efficiency nucleic acid extraction and size selection. A design of experiment (DoE) approach was used to investigate the influence of iron oxide nanoparticles (IONPs), acrylic acid (AA) monomer, and sodium dodecyl sulfate (SDS) surfactant amounts on the sizes and carboxyl group densities of PAA-IONPs. Thorough characterization by thermogravimetric analysis (TGA), attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) and vibrating sample magnetometry (VSM) highlights the importance of a low starting pH achieved by a high ratio of AA/IONPs, to yield the largest sizes (554 nm) and highest carboxyl group densities (2.13 mmol g−1) obtained in this study. An efficient DNA purification strategy is then presented using homemade beads-suspension buffer and optimized bead concentrations (17% PEG 8000, 2.5 M NaCl, and 3 mg mL−1 PAA-IONPs). This method shows comparable performance to the control (AMPure XP beads) for DNA recovery. An adjustable PAA-IONPs DNA purification system was also developed to be used for DNA-size selection at low DNA amounts (50–100 ng) with a high degree of resolution and recovery. In conclusion, this work offers an optimized PAA-IONPs synthesis protocol and a flexible DNA purification approach that will enable researchers to manipulate DNA under various conditions, holding the significant potential to benefit future molecular biology research and diagnostics.
A copper(ii) complex containing pyridine-2-carbaldehyde and its direct binding onto ethylenediamine functionalized with Fe3O4@SiO2 nanoparticles for catalytic applicationsKarimi, Masoud; Ramazani, Ali; Sajjadifar, Sami; Rezayati, Sobhan
doi: 10.1039/d3ra05649jpmid: 37800129
In the present study, a copper(ii) complex containing a pyridine-2-carbaldehyde ligand and its direct binding onto ethylenediamine functionalized with Fe3O4@SiO2 nanoparticles [Cu(ii)-Schiff base-(CH2)3-SiO2@Fe3O4] as a heterogeneous magnetic nanocatalyst can be easily prepared using a multi-step method. Next, the structural and magnetic properties of the synthesized nanoparticles were identified using Fourier-transform infrared spectroscopy (FT-IR), inductively coupled plasma (ICP), vibrating-sample magnetometry (VSM), transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA), PXRD (Powder X-ray diffraction), Brunauer–Emmett–Teller (BET), and energy-dispersive X-ray spectrometry (EDX) techniques. TEM images reveal that the average particle size distribution was found to be in the range of 45–55 nm with spherical shape. The PXRD analysis indicated that the crystallite size was found to be 35.2 nm. The synthesized nanocatalyst exhibited a very good catalytic ability in the synthesis reaction of pyran derivatives and 2-benzylidenemalononitrile derivatives. Product 2-amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydrobenzo[b]pyran 4e was achieved in 97% yield with a TON of 129.3 and a TOF of 646.6 h−1 and product 2-(4-cyanobenzylidene)malononitrile 3j was achieved in 96% yield with a TON of 128 and a TOF of 984.6 h−1. In addition, the synthesized nanocatalyst was easily separated from the reaction mixture by a magnet and used 7 consecutive times without significant loss of catalytic activity. Also, leaching of copper metal from the synthesized nanocatalyst was very insignificant for this reaction.
Cytotoxicity, anti-diabeticity, and phytocomposition investigation of Vietnamese Euphorbia tithymaloides Linn. (Euphorbiaceae)Duy Khang, Nguyen Vu; Hong Dao, Dinh Thi; Thanh Mai, Nguyen Thi; Le Quan, Tran; Thi Y Nhi, Nguyen
doi: 10.1039/d3ra05637fpmid: 37800131
In this study, the aerial parts of mature Vietnamese Euphorbia tithymaloides plants were put through cytotoxic, anti-diabetic, and phytocompositional evaluations. Specifically, four extracts (petroleum ether (PE), ethyl acetate (EA), methanol (Me), and aqueous (W)) were prepared by maceration at room temperature. All extracts, together with some isolated compounds, were investigated for cytotoxicity against some human normal and cancer cell lines (fibroblasts, HeLa, NCI-H460, HepG2, MCF-7, and Jurkat) using the standardized modified sulforhodamine B (SRB) assay. Additionally, the anti-diabetic activity of extracts and compounds was evaluated via their α-glucosidase inhibitory capacity. The obtained results indicated that Vietnamese E. tithymaloides extracts exhibited moderate cytotoxic activity, among which the PE extract possessed the highest values, on the NCI-H460 cell line. Second, the aqueous extract was revealed to possess very high α-glucosidase inhibitory activity (IC50 = 113.75 ± 14.02 μg ml−1). From the PE extract, three new jatrophane diterpenoids (named tithymal A, tithymal B, and tithymal C) and two known ones were isolated and structurally elucidated using NMR and MS spectroscopies. Noticeably, tithymal A exhibited significantly high inhibitory activity against α-glucosidase (IC50 = 10.71 ± 0.52 μg ml−1). These observations have significantly highlighted the medicinal potential of Vietnamese E. tithymaloides and expanded its scientific fascination.
Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcuminYuan, Ming; Niu, Jiangxiu; Li, Fei; Ya, Huiyuan; Liu, Xianghui; Li, Keying; Fan, Yanli; Zhang, Qiuyan
doi: 10.1039/d3ra04739cpmid: 37800130
Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR–DP–NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR–DP–NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR–DP–NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of −33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR–DP–NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR–DP–NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin–eosin staining showed that CUR–DP–NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR–DP–NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR–DP–NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.
Graphene quantum dots (GQD) and edge-functionalized GQDs as hole transport materials in perovskite solar cells for producing renewable energy: a DFT and TD-DFT studyKumar, Anjan; Sayyed, M. I.; Punina, Diego; Naranjo, Eugenia; Jácome, Edwin; Abdulameer, Maha Khalid; Albazoni, Hamza Jasim; Shariatinia, Zahra
doi: 10.1039/d3ra05438apmid: 37800128
This study investigated the potential suitability of graphene quantum dots (GQD) and certain edge-functionalized GQDs (GQD-3Xs) as hole transport materials (HTMs) in perovskite solar cells (PSCs). The criteria for appropriate HTMs were evaluated, including solubility, hole mobility, light harvesting efficiency (LHE), exciton binding energy (Eb), hole reorganization energy (λh), hole mobility, and HTM performance. It was found that several of the compounds had higher hole mobility than Spiro-OMeTAD, a commonly used HTM in PSCs. The open circuit voltage and fill factor of the suitable GQD and GQD-3Xs were found to be within appropriate ranges for HTM performance in MAPbI3 PSCs. GQD-COOH and GQD-COOCH3 were identified as the most suitable HTMs due to their high solubility, small λh, and appropriate performance.
Recent development of piezoelectric biosensors for physiological signal detection and machine learning assisted cardiovascular disease diagnosisHuang, Shunyao; Gao, Yujia; Hu, Yian; Shen, Fengyi; Jin, Zhangsiyuan; Cho, Yuljae
doi: 10.1039/d3ra05932dpmid: 37818271
As cardiovascular disease stands as a global primary cause of mortality, there has been an urgent need for continuous and real-time heart monitoring to effectively identify irregular heart rhythms and to offer timely patient alerts. However, conventional cardiac monitoring systems encounter challenges due to inflexible interfaces and discomfort during prolonged monitoring. In this review article, we address these issues by emphasizing the recent development of the flexible, wearable, and comfortable piezoelectric passive sensor assisted by machine learning technology for diagnosis. This innovative device not only harmonizes with the dynamic mechanical properties of human skin but also facilitates continuous and real-time collection of physiological signals. Addressing identified challenges and constraints, this review provides insights into recent advances in piezoelectric cardiac sensors, from devices to circuit systems. Furthermore, this review delves into the integration of machine learning technologies, showcasing their pivotal role in facilitating continuous and real-time assessment of cardiac status. The synergistic combination of flexible piezoelectric sensor design and machine learning holds substantial potential in automating the detection of cardiac irregularities with minimal human intervention. This transformative approach has the power to revolutionize patient care paradigms.
Development of two highly sensitive and selective sensor-assisted fluorescence immunoassays for trace determination of copper residues in food samplesDarwish, Ibrahim A.; Wang, Zongzhi; Darling, Ryhan J.; Alzoman, Nourah Z.
doi: 10.1039/d3ra04415gpmid: 37818275
This study describes the development of two highly sensitive and selective sensor-assisted fluorescence immunoassays for the trace determination of copper ions, Cu(ii) residues, in food samples. These assays were the microwell-based fluoroimmuoassay (FIA) and the kinetic exclusion assay (KinExA). FIA and KinExA were assisted by a microplate reader and a KinExA™ 3200 immunosensor, respectively. Both FIA and KinExA were developed utilizing the same antibody, capturing reagent, and fluorescence signal-generating reagent. The antibody was a mouse monoclonal antibody, designated as 8D66, that specifically recognized the Cu(ii)–ethylenediaminetetraacetic acid complex (Cu(ii)–EDTA) but did not recognize Cu(ii)-free EDTA. The capturing reagent was Cu(ii)–EDTA covalently linked to bovine serum albumin protein (Cu(ii)–EDTA–BSA). The fluorescence-generating reagent was an anti-mouse IgG conjugated with fluorescein isothiocyanate (IgG–FITC). Both FIA and KinExA involved competitive binding reactions between Cu(ii)–EDTA complexes, formed in the sample solution, and Cu(ii)–EDTA–BSA conjugate which has been immobilized onto microwell fluorescence assay plates (in FIA) or polymethylmethacrylate beads (in KinExA) for a limited quantity of binding sites of 8D66 antibody. The conditions of both FIA and KinExA were investigated, and the optimum procedures were established. Both FIA and KinExA were validated, and all validation parameters were acceptable. Many different metal ions that are commonly encountered in food samples did not interfere with Cu(ii) analysis by both FIA and KinExA. Both assays were applied to the determination of Cu(ii) in food samples with satisfactory accuracy and precision. Both assays were compared favorably with inductively coupled plasma atomic emission spectroscopy. Comparative evaluation of FIA and KinExA revealed that KinExA had higher sensitivity and better precision than FIA, whereas, both assays had comparable accuracy. Both FIA and KinExA were superior to the existing atomic spectrometric methods for Cu(ii). The proposed FIA and KinExA are anticipated to effectively contribute to assessing Cu(ii) concentrations and controlling the exposure of humans to its potential toxicities.