Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the ...electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex
), electron-neutral (complex
), and electron-donating (complex
) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex
) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.
Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against ...human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds
(IC
= 1.51 ± 0.09 µM) and
(IC
= 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound
showed considerable cytotoxicity against both tested cell lines, MCF7 (IC
= 5.46 ± 0.71 µM) and A2780 (IC
= 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds
(IC
= 0.245 µM) and
(IC
= 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC
= 0.131 µM). A molecular docking study of
and
confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.
An efficient and practical method for the synthesis of 2,6-diaryl-4-oxo-
,
'-di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide is described in this present study, which occurs through a double Michael ...addition reaction between diamide and various dibenzalacetones. The reaction was carried out in dichloromethane (DCM) in the presence of 1,8-diazabicyclo5.4.0undec-7-ene (DBU). The anticancer activities of the synthesized compounds were evaluated in several cancer cell lines, including MCF-7, MDA-MB-231, SAS, PC-3, HCT-116, HuH-7 and HepG2 cells. From these experiments, we determined that MDA-MB-231 was the most sensitive cancer cell line to the compounds
,
,
,
and
, which exhibited variable anticancer activities (
IC
= 5 ± 0.25 µM > 3e IC
= 5 ± 0.5 µM >
IC
= 7 ± 1.12 µM >
IC
= 18 ± 0.87 µM >
IC
= 45 ± 3 µM). Of these,
(substituted
-trifluoromethylphenyl and chloropyridine) showed good potency (IC
= 6 ± 0.78 µM) against HCT-116 colorectal cancer cells and exhibited high toxicity against HuH-7 liver cancer cells (IC
= 4.5 ± 0.3 µM). These values were three times higher than the values reported for cisplatin (IC
of 8 ± 0.76 and 14.7 ± 0.5 µM against HCT-116 and HuH-7 cells, respectively). The highest α-glucosidase inhibitory activity was detected for the
,
and
compounds. The details of the binding mode of the active compounds were clarified by molecular docking studies.
In this paper, a highly sensitive graphene-based multiple-layer (BK
/Au/PtSe
/Graphene) coated surface plasmon resonance (SPR) biosensor is proposed for the rapid detection of the novel Coronavirus ...(COVID-19). The proposed sensor was modeled on the basis of the total internal reflection (TIR) technique for real-time detection of ligand-analyte immobilization in the sensing region. The refractive index (RI) of the sensing region is changed due to the interaction of different concentrations of the ligand-analyte, thus impacting surface plasmon polaritons (SPPs) excitation of the multi-layer sensor interface. The performance of the proposed sensor was numerically investigated by using the transfer matrix method (TMM) and the finite-difference time-domain (FDTD) method. The proposed SPR biosensor provides fast and accurate early-stage diagnosis of the COVID-19 virus, which is crucial in limiting the spread of the pandemic. In addition, the performance of the proposed sensor was investigated numerically with different ligand-analytes: (i) the monoclonal antibodies (mAbs) as ligand and the COVID-19 virus spike receptor-binding domain (RBD) as analyte, (ii) the virus spike RBD as ligand and the virus anti-spike protein (IgM, IgG) as analyte and (iii) the specific probe as ligand and the COVID-19 virus single-standard ribonucleic acid (RNA) as analyte. After the investigation, the sensitivity of the proposed sensor was found to provide 183.33°/refractive index unit (RIU) in SPR angle (
) and 833.33THz/RIU in SPR frequency (SPRF) for detection of the COVID-19 virus spike RBD; the sensitivity obtained 153.85°/RIU in SPR angle and 726.50THz/RIU in SPRF for detection of the anti-spike protein, and finally, the sensitivity obtained 140.35°/RIU in SPR angle and 500THz/RIU in SPRF for detection of viral RNA. It was observed that whole virus spike RBD detection sensitivity is higher than that of the other two detection processes. Highly sensitive two-dimensional (2D) materials were used to achieve significant enhancement in the Goos-Hänchen (GH) shift detection sensitivity and plasmonic properties of the conventional SPR sensor. The proposed sensor successfully senses the COVID-19 virus and offers additional (1 + 0.55) ×
times sensitivity owing to the added graphene layers. Besides, the performance of the proposed sensor was analyzed based on detection accuracy (DA), the figure of merit (FOM), signal-noise ratio (SNR), and quality factor (QF). Based on its performance analysis, it is expected that the proposed sensor may reduce lengthy procedures, false positive results, and clinical costs, compared to traditional sensors. The performance of the proposed sensor model was checked using the TMM algorithm and validated by the FDTD technique.
Several photophysical properties of chromophores depend crucially on intermolecular interactions. Thermally‐activated delayed fluorescence (TADF) is often influenced by close packing of the ...chromophore assembly. In this context, the metal‐organic framework (MOF) approach has several advantages: it can be used to steer aggregation such that the orientation within aggregated structures can be predicted using rational approaches. We demonstrate this design concept for a DPA‐TPE (diphenylamine‐tetraphenylethylene) chromophore, which is non‐emissive in its solvated state due to vibrational quenching. Turning this DPA‐TPE into a ditopic linker makes it possible to grow oriented MOF thin films exhibiting pronounced green electroluminescence with low onset voltages. Measurements at different temperatures clearly demonstrate the presence of TADF. Finally, this work reports that the layer‐by‐layer process used for MOF thin film deposition allows the integration of the TADF‐DPA‐TPE in a functioning LED device.
A crystalline, oriented thin film with green electroluminescence is illustrated. Enforced by SURMOF assembly, controlled aggregation of the DPA‐TPE linker chromophore turned‐on TADF process, boosting the luminance of the crystalline thin film.
Breast cancer is one of the leading cancers among the Bangladeshi women. Coping helps these patients to adjust with this life-changing disease. Each individual has unique and different coping ...mechanism. But we know a little regarding their coping strategies. This study aims to explore the different coping strategies adopted by the women with metastatic (stage IV) breast cancer attending the palliative care unit and their relationship with the common mental health issues like anxiety and depression.
This cross-sectional study was conducted among 95 patients with metastatic (stage IV) breast cancer attending the Department of Palliative Medicine, Bangabandhu Sheikh Mujib Medical University, Bangladesh from April 2021 to September 2021. Data was collected by face-to-face interview using a structured questionnaire adapted from Hospital Depression and Anxiety Scale (HADS), Brief COPE inventory and Eastern Cooperative Oncology Group (ECOG) performance scale. Pearson correlation test was used to find the relationships between various domains of coping strategies and psychological variables. Correlation matrix was done to observe the internal correlation among different coping strategies. Kruskal-Wallis H test was done to find the relationship between different coping strategies and ECOG performance status.
The mean age of the respondents was 48.9 ± 9.9 years. Most of them were married (94.7%), Muslim (92.6%) and homemakers (82.1%). Commonly used coping strategies by the patients were: acceptance (median 10; IQR 10), religion (median 9; IQR 8-10) and instrumental support (median 9; IQR 6-10). Significantly strong positive correlation was found between emotional and instrumental support (R = 0.7; p = 0.01), planning, acceptance and active coping (R = 0.7; p = 0.01); behavioral disengagement, self distraction and denial (R = 0.5; p = 0.01). Significantly fair negative correlation was observed between active coping and depression (R = -0.4, p <0.001). Patients with better performance status on ECOG scale (Grade 0-2) leaned more on the positive coping strategies like instrumental support, emotional support, positive reframing and venting.
Different coping strategies, especially positive coping helps the patients to adapt with their disease over time. All women suffering from breast cancer should be routinely screened and assessed for psychological distress and ensure early intervention and management to promote a better quality of life.
In this study, we present a comprehensive investigation of 2-amino-4,6-diphenylnicotinonitriles (APNs,
-
), including their synthesis, cytotoxicity against breast cancer cell lines, and photophysical ...properties. Compound
demonstrates exceptional cytotoxicity, surpassing the potency of Doxorubicin. The fluorescence spectra of the synthesized
-
in different solvents reveal solvent-dependent shifts in the emission maximum values, highlighting the influence of the solvent environment on their fluorescence properties. A quantum chemical TD-DFT analysis provides insights into the electronic structure and fluorescence behavior of
-
, elucidating HOMO-LUMO energy gaps, electronegativity values, and dipole moments, contributing to a deeper understanding of their electronic properties and potential reactivity. These findings provide valuable knowledge for the development of APNs (
-
) as fluorescent sensors and potential anticancer agents.
A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) and human ovarian carcinoma (A2780) cell ...lines. Cytotoxicity of the most tested compounds was 2- to 30-fold more than the positive control lapatinib (IC
50
of 2j = 3.79 ± 0.96; 3j = 0.20 ± 0.02; and lapatinib = 5.9 ± 0.74) against MCF7 cell lines except two compounds (IC
50
of 2 b = 15.72 ± 0.07 and 2e = 14.88 ± 0.99). On the other hand, cytotoxicity was 4 − 87 folds (IC
50
of 3a = 3.00 ± 1.20; 3 g = 0.14 ± 0.03) more the positive control lapatinib (IC
50
= 12.11 ± 1.03) against A2780 cell lines except compound 2e (IC
50
= 16.43 ± 1.80). Among the synthesised quinazolin-4(3H)-one derivatives, potent cytotoxic 2f-j and 3f-j were investigated for molecular mechanism of action. Inhibitory activities of the compounds were tested against multiple tyrosine protein kinases (CDK2, HER2, EGFR and VEGFR2) enzymes. As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. However, in case of HER2, compounds 2i act as ATP non-competitive type-II inhibitor and 3i act as ATP competitive type-I inhibitor. Docking results of known inhibitors were compared with synthesised compounds and found synthesised 2i and 3i are superior than the known inhibitors in case of interactions. In addition, in silico drug likeness properties of quinazolin-4(3H)-one derivatives showed better predicted ADME values than lapatinib.
ive text summarization is a process of making a summary of a given text by paraphrasing the facts of the text while keeping the meaning intact. The manmade summary generation process is laborious and ...time‐consuming. We present here a summary generation model that is based on multilayered attentional peephole convolutional long short‐term memory (MAPCoL; LSTM) in order to extract ive summaries of large text in an automated manner. We added the concept of attention in a peephole convolutional LSTM to improve the overall quality of a summary by giving weights to important parts of the source text during training. We evaluated the performance with regard to semantic coherence of our MAPCoL model over a popular dataset named CNN/Daily Mail, and found that MAPCoL outperformed other traditional LSTM‐based models. We found improvements in the performance of MAPCoL in different internal settings when compared to state‐of‐the‐art models of ive text summarization.
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