A novel SpaSA based hyper-parameter optimized FCEDN with adaptive CNN classification for skin cancer detection.

Skin cancer is the most prevalent kind of cancer in people. It is estimated that more than 1 million people get skin cancer every year in the world. The effectiveness of the disease's therapy is significantly impacted by early identification of this illness. Preprocessing is the initial detecting stage in enhancing the quality of skin images by removing undesired background noise and objects. This study aims is to compile preprocessing techniques for skin cancer imaging that are currently accessible. Researchers looking into automated skin cancer diagnosis might use this article as an excellent place to start. The fully convolutional encoder-decoder network and Sparrow search algorithm (FCEDN-SpaSA) are proposed in this study for the segmentation of dermoscopic images. The individual wolf method and the ensemble ghosting technique are integrated to generate a neighbour-based search strategy in SpaSA for stressing the correct balance between navigation and exploitation. The classification procedure is accomplished by using an adaptive CNN technique to discriminate between normal skin and malignant skin lesions suggestive of disease. Our method provides classification accuracies comparable to commonly used incremental learning techniques while using less energy, storage space, memory access, and training time (only network updates with new training samples, no network sharing). In a simulation, the segmentation performance of the proposed technique on the ISBI 2017, ISIC 2018, and PH2 datasets reached accuracies of 95.28%, 95.89%, 92.70%, and 98.78%, respectively, on the same dataset and assessed the classification performance. It is accurate 91.67% of the time. The efficiency of the suggested strategy is demonstrated through comparisons with cutting-edge methodologies.

Peptidomimetics for CVD screened via TRADD-TRAF2 complex interface assessments.

The main aim of this study is to screen and develop Peptidomimetics to treat atherosclerosis (AS) which is a Cardio Vascular Disease (CVD). Peptidomimetics were obtained from the protein-protein interaction interface of TRADD (Tumor necrosis factor receptor type 1-associated DEATH domain protein) and TRAF2 (TNF receptor-associated factor 2) complex. TRADD-TRAF2 interaction is critical in AS pathogenesis since it assists a series of signal transducers that activate NF-κB. Conceptually, the triggered NF-κB makes an extensive amount of nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS), which boons the progress of AS. The examined TRADD-TRAF2 complex (PDB ID: 1F3V) and its interaction details revealed that the sequence range W11-G165 of TRADD highly interacts with TRAF2. The sequence range W11-G165 was selected for the design and preparation of the inhibitory peptide in silico. The selected sequence was mutated with the alanine scanning method to have a range of inhibitory peptides. With the help of different in silico tools, the top three, namely MIP11-25 L, MIP131-143 h, and MIP149-164 m peptides showed the best interaction with the critical residues of TRAF2. Thus, these three peptides were used for generating peptidomimetics using pepMMsMIMIC, a peptidomimetics virtual screening tool. Around 600 peptidomimetics were identified & and retrieved for further screening by employing molecular docking tools and MD (Molecular Dynamics) simulations. Density Functional Theory (DFT) and ADMET predictions were applied to validate the screened peptidomimetics druggability. In the results, peptidomimic compounds MMs03918858 and MMs03927281 with binding energy values of -9.6 kcal/mol and - 9.1 kcal/mol respectively were screened as the best and are proposed for further pre-clinical studies.

Functional Properties of Grapefruit Seed Extract Embedded Blend Membranes of Poly(vinyl alcohol)/Starch: Potential Application for Antiviral Activity in Food Safety to Fight Against COVID-19.

The poly(vinyl alcohol) (PVA) and starch-based polymeric films with a ratio of 2:8 were prepared using solution casting followed by a solvent evaporation method. Four types of membranes with varied concentrations of grapefruit seed extract (GSE) i.e., 2.5-10 wt% was incorporated in the films. The prepared membranes were assessed for transparency test, mechanical properties, surface morphology, permeability test for O2, and antimicrobial properties. The PVA/starch-10% GSE loaded film showed excellent mechanical properties showing highest 1344 ± 0.7% elongation at break but poor optical transparency with 53.8% to 68.61%. The Scanning Electron Microscopic study reveals the good compatibility between the PVA, Starch, and GSE. The gas permeability test reveals that the prepared films have shown good resistance to the O2 permeability 0.0326-0.316 Barrer at 20 kg/cm2 feed pressure for the prepared membranes showing excellent performance. By adding the little amount of GSE into the PVA/starch blend membranes showed promising antimicrobial efficacy against MNV-1. For 4 h. incubation, PVA/starch blend membranes containing 2.5%, 5%, and 10% GSE caused MNV-1 reductions of 0.92, 1.89, and 2.27 log PFU/ml, respectively. Similarly, after 24 h, the 5% and 10% GSE membranes reduced MNV-1 titers by 1.90 and 3.26 log PFU/ml, respectively. Antimicrobial tests have shown excellent performance to resist microorganisms. The water uptake capacity of the membrane is found 72% for the PVA/starch pristine membrane and is reduced to 32% for the 10% GSE embedded membrane. Since the current pandemic situation due to COVID-19 occurred by SARSCOV2, the prepared GSE incorporated polymeric blend films are the rays of hope in the packaging of food stuff.

Growth Characteristics of Female Radiation/Clinical Oncologists in South Asia: Assessment of Gender Neutrality and Leadership Position.

AIM: To evaluate the temporal growth pattern of female radiation/clinical oncologists (FRCOs) and, if applicable, predict the gender neutrality in different countries of South Asia. MATERIALS AND METHODS: South Asia is composed of Afghanistan, Bhutan, Maldives, Bangladesh, India, Nepal, Pakistan and Sri Lanka. The growth pattern of FRCOs in the latter five countries having radiation oncology facilities was evaluated from respective national registration data. Based on the average annual differential growth rate, together with the already existing female and male radiation/clinical oncologists (MRCOs), the cumulative numbers of FRCOs and MRCOs were forecasted for the next 10 years. The data regarding FRCOs in a leadership position were also calculated from different sources. RESULTS: The total number of radiation/clinical oncologists in the region was 4074, of which 91.8% were in India, because of its vast population. The overall number of FRCOs and MRCOs stood at 1370 and 2704, with a 1:2 female:male ratio. The average incremental annual growth of FRCOs in India was the highest (12.7 persons/year) and Nepal was the lowest (0.4 persons/year), with no data from Pakistan. If the current growth rate is sustained, Indian gender neutrality will be achieved by 2027-2030. In other countries, gender neutrality is unlikely to be achieved in the near future. With regards to leadership positions, 56-77 radiation oncology departments in India, one each in Bangladesh and Sri Lanka are headed by FRCOs, whereas Nepal and Pakistan have none. CONCLUSIONS: With the current growth rate of FRCOs and MRCOs, India will achieve gender parity within a decade; however, the rest of the countries will not achieve this in the near future. Analysis of radiation/clinical oncologists' registration data with their respective national bodies revealed an encouraging growth in the number of FRCOs as against their male counterparts in the last 5 years, compared with previous decades, especially in Bangladesh, Sri Lanka and India. Sri Lanka show high gender neutrality and adopted a multi-tasking and holistic approach of clinical oncology practices as also seen in Scandinavian countries. Such practice may be helpful to improve gender equality in radiation/clinical oncology practice for the other countries in the South Asian region.

Crystal structure, spectral investigations, DFT and antimicrobial activity of brucinium benzilate (BBA).

The unreported brucinium benzilate (BBA) crystal and Hirshfeld surface analysis indicated the influence of intramolecular hydrogen bonding network on the crystal structure. Protonation occurs at the tertiary nitrogen as it is the most basic site. The protonated N-H+ proton was observed at 7.08 ppm and the benzilate carbon COO- at 178.41 ppm. Molecular electrostatic potential (MEP) studies showed the electron-rich and electron-deficient sites in the molecule for understanding BBA interaction with an enzyme. Frontier molecular orbital (FMO) studies indicated that BBA molecule is thermodynamically stable and the HOMO-LUMO energy gap was found to be 4.454 eV. The highest interaction has the energy (322.86 kcal/mol) between tertiary ammonium N(LP) and H+. Inhibition tests showed that brucinium benzilate inhibits Bacillus cereus and Salmonella typhimurium bacteria. ADMET properties indicated that BBA has drug characteristics in binding plasma protein.

Synthesis, Spectral Characterization and Biological Activities of Co(II) and Ni(II) Mixed Ligand Complexes.

2,4-Dinitrophynylhydrazine and two thiocyanate ions in a (M:L1:L2) 1:2:2 molar ratio was synthesized in the complexes of Co(II) and Ni(II). The prepared compounds were identified through a C.H.N.S. analysis, conductivity measurements, powder X-ray diffraction (PXRD), the infrared spectrum, and a UV-visible spectrum analysis, in addition to the magnetic properties being measured. The measurements of the molar conductance implieda nonelectrolytic nature of compounds Co(II) and Ni(II). The magnetic susceptibility, as well as electronic spectra, represented all the metal complexesthroughoctahedral geometry, respectively. The PXRD patterns suggested that all the complexes were an orthorhombic system with unit cell parameters. The in-vitro biological activity of the ligand and the metal complexes were screened against the Gram-positive and negative pathogenic bacteria Staphylococcus aureus, Bacillus subtilis, Pseudomonas, aeruginosa and Escherichia coli, as well as the fungal species of Aspergillusniger and Candida albicans.Thus, the metal complexes showeda high efficiency of antimicrobial activity compared with the ligand. Furthermore, applications of the ligand, as well as the metal complexes, were tested for in-vitro antioxidant potential in aDPPH assay. The results showed that the activity of the metal complexes with the in-vitro antioxidant was more active than that of 2,4-dinitrophenylhydrazine(DNPH).

Foliar application of chitosan nanoparticle improves yield, mineral content and boost innate immunity in finger millet plants.

The aim of the present study is to evaluate the potential of chitosan and chitosan nanoparticles (ChNPs) in enhancing the growth and yield of finger millet under greenhouse condition. Foliar application of ChNPs significantly enhanced the growth, yield and mineral content (Fe, Zn, Mn, P, Ca, Mg) when compared to the chitosan and untreated control. ChNPs also induced several defense related enzymes (chitinase, ß-1,3 glucanase, chitosanase, protease inhibitors, peroxidase, polyphenol oxidase) in leaves of finger millet plants their by enhancing the innate immune response. This quantitative difference in defense enzymes was also detected qualitatively on polyacrylamide gels. Our results suggest that ChNPs application can be used as an ecofriendly approach to enhance yield and mineral content in finger millet for sustainable production.

Socio-economic demands and challenges for non-invasive disease diagnosis through a portable breathalyzer by the incorporation of 2D nanosheets and SMO nanocomposites.

Breath analysis for non-invasive clinical diagnostics and treatment progression has penetrated the research community owing to the technological developments in novel sensing nanomaterials. The trace level selective detection of volatile organic compounds (VOCs) in breath facilitates the study of physiological disorder and real-time health monitoring. This review focuses on advancements in chemiresistive gas sensor technology for biomarker detection associated with different diseases. Emphasis is placed on selective biomarker detection by semiconducting metal oxide (SMO) nanostructures, 2-dimensional nanomaterials (2DMs) and nanocomposites through various optimization strategies and sensing mechanisms. Their synergistic properties for incorporation in a portable breathalyzer have been elucidated. Furthermore, the socio-economic demands of a breathalyzer in terms of recent establishment of startups globally and challenges of a breathalyzer are critically reviewed. This initiative is aimed at highlighting the challenges and scope for improvement to realize a high performance chemiresistive gas sensor for non-invasive disease diagnosis.

Exploring the influence of varying pH on structural, electro-optical, magnetic and photo-Fenton properties of mesoporous ZnFe2O4 nanocrystals.

An economically viable and superficial technique was indorsed to yield ZnFe2O4 nanocrystals in the system to investigate the impact of pH variation on the optical, structural, electrical, and magnetic properties of as-prepared nanocrystals. The as-synthesized ZnFe2O4 nanocrystals were premeditated with the application protracted to degradation of Methylene blue organic dye. The results specify that the pH plays the utmost decisive facet in photo-Fenton recital. From XRD (X-Ray diffraction) analyses, it was confirmed that as-synthesized nanocrystals belong to a cubic Fd3m crystal phase. The crystallite size was also determined by the Scherrer formula and it was noticed that as the pH rises the crystallite size also increased. FT-IR (Fourier Transform Infrared) analysis depicts two absorption peaks âˆ¼ 500 and ∼600 cm-1 that represents tetrahedral (Td) and octahedral (Oh) sites. Using TEM (Transmission Electron Microscopy), the morphology was observed to be spherical particles with some agglomeration. Photoluminescence and UV-visible spectral studies were performed to investigate the optical properties. The bandgap energy was seen to decrease as the pH increased. Using BET analysis, the surface area for the as-synthesized samples was found to decrease on increasing the pH. The reaction results showed that the ZnFe2O4 has good photocatalytic activity, which can be attributed to high surface area and pore volume, and large pore size. The ZnFe2O4 produced by the co-precipitation route exhibited promising photocatalytic activity for the removal of textile dye, reaching nearly 99.2% of decolorization at 100 min. Therefore, ZnFe2O4 particles rapidly prepared by the co-precipitation route have the potential for use in treatment of textile wastewater by the heterogeneous photo-Fenton process. With the help of VSM analysis, the coercivity and other magnetic properties were determined for the as-synthesized nanocrystal with plays a significant role in photocatalytic recyclability, which intends to premediate that the prepared nanocrystals can be used in industrial persistence.

Characterization and Performance Evaluation of the First-Proton Therapy Facility in India.

PURPOSE: The purpose of this study is to evaluate the performance characteristic of volumetric image-guided dedicated-nozzle pencil beam-scanning proton therapy (PT) system. MATERIALS AND METHODS: PT system was characterized for electromechanical, image quality, and registration accuracy. Proton beam of 70.2-226.2 MeV was characterized for short- and long-term reproducibility in integrated depth dose; spot profile characteristics at different air gap and gantry angle; positioning accuracy of single and pattern of spot; dose linearity, reproducibility and consistency. All measurements were carried out using various X-ray and proton-beam specific detectors following standard protocols. RESULTS: All electro-mechanical, imaging, and safety parameters performed well within the specified tolerance limit. The image registration errors along three translation and three rotational axes were ≤0.5 mm and ≤0.2° for both point-based and intensity-based auto-registration. Distal range (R90) and distal dose fall-off (DDF) of 70.2-226.2 MeV proton beams were within 1 mm of calculated values based on the international commission on radiation units and measurements 49 and 0.0156× R90, respectively. The R90 and DDF were reproducible within a standard deviation of 0.05 g/cm2 during the first 8 months. Dose were linear from 18.5 (0.011 MU/spot) to 8405 (5 MU/spot) MU, reproducible within 0.5% in 5 consecutive days and consistent within 0.8% for full rotation. The cGy/MU for 70.2-226.2MeV was consistent within 0.5%. In-air X(Y) spot-sigma at isocenter varies from 2.96 (3.00) mm to 6.68 (6.52) mm for 70.2-226.2 MeV. Maximum variation of spot-sigma with air-gap of ±20 cm was ±0.36 mm (5.28%) and ±0.82 mm (±12.5%) along X- and Y-direction and 3.56% for full rotation. Relative spot positions were accurate within ±0.6 mm. The planned and delivered spot pattern of known complex geometry agreed with (γ%≤1) for 1% @ 1 mm >98% for representative five-proton energies at four gantry angle. CONCLUSION: The PT-system performed well within the expected accuracy level and consistent over a period of 8 months. The methodology and data presented here may help upcoming modern PT center during their crucial phase of commissioning.

p-TSA.H2O mediated one-pot, multi-component synthesis of isatin derived imidazoles as dual-purpose drugs against inflammation and cancer.

A novel one-pot multicomponent reaction was performed to synthesize different imidazole and benzotriazole (BTA) isatin-based medicinally important compounds using (p-TSA·H2O) as an economical and operative acid catalyst. The yield of the products was found to be up to a maximum of 92% when using this catalyst. Antioxidant, anti-breast cancer and anti-inflammatory activities of these 13 isatin-based derivatives (named as 5a-m) were assessed. The inhibitory effects of these compounds were tested in vitro against cyclooxygenase-2 (COX-2, an enzyme responsible for inflammation) and phosphoinositide-3 kinase (PI3K, a key enzyme in breast cancer). "Among the 13 isatin-based Imidazole derivatives, five compounds (5a, 5d, 5f, 5 k and 5l) were found to exhibit anti-inflammatory as well as anti-cancer activity, which was validated using HRBC stabilization assay (to show anti-inflammatory activity) and cytotoxicity in MCF-7 (breast cancer cell line) to provide proof for anti-cancer property of the compounds". The molecular interactions between the two enzymes were probed using molecular docking. Structure-Activity Relationship (SAR) and ADMET prediction results were also useful to screen the most effective imidazole derivatives and to establish them as putative COX-2 inhibitors/anti-inflammatory drugs. These selected compounds which showed appreciable activity against COX-2 and PI3K are promising drug candidates for the treatment of breast cancer and inflammation which is often associated with breast cancer pathophysiology.

Synthesis and discovery of pyrazolo-pyridine analogs as inflammation medications through pro- and anti-inflammatory cytokine and COX-2 inhibition assessments.

This article briefs about the efforts taken to synthesis, characterize and develop (E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-ylmethylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine and their analogs. In the two-step reaction, the first step is the synthesis of (3Z,5E)-1-methyl-3,5-bis(thiophen-2-ylmethylene)piperidin-4-one derivatives (3a-l) by stirring the mixture of 1-methylpiperidin-4-one and substituted thiophene-carbaldehydes in presence of methanol. In the second and final step, compounds 3a-l were refluxed with phenyl-hydrazine to achieve the target compounds (E)-5-methyl-2-phenyl-3-(thiophen-2-yl)-7-(thiophen-2-ylmethylene)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine and their analogs (5a-l) in good yield. These compounds were used to assess their inflammation regulation properties in macrophages by executing quantitative pro-inflammatory and anti-inflammatory proteins such as TNF-α, IL-1ß, IL6, and IL-10 respectively. In silico and in vitro COX-2 inhibition studies helped to understand the molecular interaction or plausible mechanism during the inflammation regulation that showed by the compounds. In the results, among the 12-member family of pyrazolo-pyridines (5a-l), 5a, 5b, 5g, and 5j were showed excellent in silico binding affinity (1-10 nM), least binding energy (-12.45 to -14.27 kcal/mol) and in vitro COX-2 inhibition (relative percentage activity maximum 96.42%). Thus, these compounds perhaps to be future anti-inflammatory drugs.

Synthesis and discovery of triazolo-pyridazine-6-yl-substituted piperazines as effective anti-diabetic drugs; evaluated over dipeptidyl peptidase-4 inhibition mechanism and insulinotropic activities.

A family of 12 triazolo-pyridazine-6-yl-substituted piperazines (5a-l) was synthesized and evaluated for their Dipeptidyl peptidase-4 (DPP-4) inhibition potentials in order to develop them as anti-diabetic medications. In the two-step synthesis process, 6-chloro-3-(m-tolyl)-[1,2,4]triazolo[4,3-b]pyridazine was synthesized with one-pot mode using pyridine, 3,6-dichloropyridazine 5-(3-methyl-phenyl)tetrazole in toluene. Conjugating corresponding 2° amines with 6-chloro-3-(m-tolyl)-[1,2,4]triazolo[4,3-b]pyridazine afforded the target triazolo-pyridazine-6-yl-substituted piperazines (5a-l). DPP-4 inhibition potential of these compounds was testified in silico and in nitro along with their insulinotropic activities in 832/13 INS-1 cells. H2O2 radical scavenging assay and MTT assay were conducted to assess the antioxidant and cytotoxicity of these compounds respectively. Molecular docking and ELISA based enzyme inhibition assay results revealed the strong inhibition potential of the target compounds. MTT assay results indicated a maximum dose of 2.5 nM (IC50 1.25 nM) could be used and above this level vital for the cells. Compounds 5a, 5c, 5g and 5i were found with excellent antioxidant and insulinotropic activity up to 99%.

Ni0.4Cu0.2Zn0.4TbxFe2-xO4 nanospinel ferrites: Ultrasonic synthesis and physical properties.

The Fe3+ ions were replace with Tb3+ ions as highly paramagnetic rare earth element within the structure of Ni0.4Cu0.2Zn0.4Fe2O4 nano-spinel ferrites (NSFs). The structural, magnetic, spectroscopic and optic properties have been studied in details. All products have been synthesized via ultrasonic approach via Qsonica ultrasonic homogenizer, frequency: 20 kHz and power: 70 W for 60 min. No annealing or calcination process was applied for any product. The microstructural analysis of products has been done via X-ray powder diffractometry (XRD) which presented the cubic spinel structure with nanosized distribution of all. The cubic morphology of all products were confirmed by both HR-TEM and FE-SEM. Optical band gap (Eg) values were assessed by applying %DR (percent diffuse reflectance) analysis and Kubelka-Munk theory. The Tauc schemes showed that Eg values are in a narrow range (1.87-1.98 eV). The quadrupole splitting, line width, hyperfine magnetic field, isomer shift values and cation distribution have been determined from 57Fe Mossbauer analysis. The magnetic properties of various nanoparticles have been obtained from VSM (vibration sample magnetometer) measurements at 10 and 300 K (RT). The magnetic results revealed superparamagnetic and soft ferromagnetic traits at 10 and 300 K, respectively. Ms (saturation magnetization) and Mr (remanence) initially increase with increasing Tb3+ substituting level up to x = 0.06 then diminish for further x values. Hc (coercivity) shows an opposite variation tendency of Ms and Mr. The observed magnetic traits are deeply discussed in relation with the structure, morphology, magnetic moments and cation distributions.

Discovery, synthesis and molecular substantiation of N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides as anticancer agents.

The effort was taken to develop a series of benzothiazole and quinoline fused bioactive compounds obtained through a four-step synthetic route using a range of substituted acetoacetanilides. Achieved N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides (6a-l) were produced up to 96% of yield while the eco-friendly p-TSA used as a catalyst. Further, the anticancer activity of these compounds was determined using a range of cancer cell lines starting from MCF-7 (Breast cancer), HCT-116 (Colon cancer), PC-3 & LNCaP (Prostate) and SK-HEP-1 (Liver cancer). Present study compounds were also testified for antioxidant properties prior to anticancer studies since the Reactive Oxygen Species (ROS) being vital in cancer development. To determine the cell membrane stability effects of the compounds, human red blood cells (HRBC) based membrane protection assay was determined. In the results, compounds 6a-l were able to produce a dominated result values over PC3 cell lines (Prostate cancer) than the other cell lines used in this study. Since the connectivity of human germ cell alkaline phosphatase (hGC-ALP) in the development of prostate cancer is known, the most active compounds were evaluated for the hGC-ALP inhibition in order to ensure a mechanism of anticancer action of these compounds. The mode of interaction and binding affinity of these compounds was also investigated by a molecular docking study. In the results, 6d, 6i, 6k, and 6l were found with least IC50 values <0.075 µM and highest relative activity of 92%, 90%, and 96% respectively. The need for further animal model evaluation and pre-clinical studies recognized.

Identification, isolation and characterization of dolutegravir forced degradation products and their cytotoxicity potential.

Dolutegravir was approved by USFDA, Canada and European regulatory authorities as antiretroviral medication. In this article, DLG forced degradation studies as per the International Council for Harmonization (ICH) prescribed stress conditions was conducted and the resulting degradants were fully characterized. DLG was stable in basic, thermal and photolytic stress conditions, whereas DLG was found to unstable in acidic and oxidative conditions. One degradant each from acid and peroxide treated solutions was resolved on LC-MS and labelled as DP-1 and DP-2 with RT 1.80 min and 1.41 min, respectively. DP-1 and DP-2 were isolated by preparative HPLC with C18 column using gradient elution method. Subsequently DP-1 and DP-2 peaks were subjected to HRMS for accurate mass. Molecular mass of DP-1 and DP-2 were m/z 420.1379 (positive mode) and m/z 214.0319 (negative mode), respectively. Further, DP-1 & DP-2 were subjected to NMR spectroscopic analysis (including 2D) for structural confirmation. DP-1 was identified as N-(2,4-difluorobenzyl)-9-hydroxy-2-(4-hydroxybutan-2-yl)-1,8-dioxo-2,8-dihydro-1H-pyrido[1,2-a]pyrazine-7-carboxamide and it is earlier reported by Gudisela et al. [19] as DLG process impurity. DP-2 was identified as 2-(2,4difluorobenzylamino)-2-oxoacetic acid which is novel DLG degradant and not reported earlier to the best of our knowledge. DLG along its forced degradation products were found to be non-cytotoxic in in vitro assay conditions using HepG2 cells.

Magnetic Attributes of NiFe2O4 Nanoparticles: Influence of Dysprosium Ions (Dy3+) Substitution.

This paper reports the influence of dysprosium ion (Dy3+) substitution on the structural and magnetic properties of NiDyxFe2-xO4 (0.0 ≤ x ≤ 0.1) nanoparticles (NPs) prepared using a hydrothermal method. The structure and morphology of the as-synthesized NPs were characterized via X-ray diffraction (XRD), scanning and transmission electron microscope (SEM, and TEM) analyses. 57Fe Mössbauer spectra were recorded to determine the Dy3+ content dependent variation in the line width, isomer shift, quadrupole splitting, and hyperfine magnetic fields. Furthermore, the magnetic properties of the prepared NPs were also investigated by zero-field cooled (ZFC) and field cooled (FC) magnetizations and AC susceptibility measurements. The MZFC (T) results showed a blocking temperature (TB). Below TB, the products behave as ferromagnetic (FM) and act superparamagnetic (SPM) above TB. The MFC (T) curves indicated the existence of super-spin glass (SSG) behavior below Ts (spin-glass freezing temperature). The AC susceptibility measurements confirmed the existence of the two transition temperatures (i.e., TB and Ts). Numerous models, e.g., Neel-Arrhenius (N-A), Vogel-Fulcher (V-F), and critical slowing down (CSD), were used to investigate the dynamics of the systems. It was found that the Dy substitution enhanced the magnetic interactions.

Cu-mediated synthesis of differentially substituted diazepines as AChE inhibitors; validation through molecular docking and Lipinski's filter to develop novel anti-neurodegenerative drugs.

A highly efficient Cu-mediated route for the synthesis of fused [1,2,3]triazolo[1,4]diazepines has been developed by azidation-cyclization of 2-bromo-N-propargylamines in a one-pot fashion. The key highlight of the present work is that the 2-bromo-N-propargylamines are prepared through the A3-reaction of cyclic amines such as isoquinoline and decarboxylative coupling of proline and pipecolinic acid with 2-bromo benzaldehyde and alkyne. As preliminary, these compounds were analyzed for their most probable bioactivity using various in silico tools. The recognized anti-neurodegenerative activity potential was assessed by molecular docking, AChE inhibition activity in erythrocytes and DPPH radical scavenging activity potentials possessed by the compounds. With a relative AChE inhibition activity of 97% (IC50 0.25 ±â€¯0.02 µM), compound 5d identified as the most active compound. Druggability of these compounds also evaluated through Lipinski's filter and other ADMET tools for the betterment of selective execution of in vitro and in vivo activities of the screened compounds cautiously.

Discovery and synthesis of 2-amino-1-methyl-1H-imidazol-4(5H)-ones as GPCR ligands; an approach to develop breast cancer drugs via GPCR associated PAR1 and PI3Kinase inhibition mechanism.

Efforts were taken to synthesis and characterize 2-amino-1-methyl-1H-imidazole-4(5H)-one derivatives (4a-u) through a four-step reaction. The achieved compounds in remarkable yield have characterized through standard analytical techniques such as FTIR, LC-MS, NMR, HRMS, and elemental analysis. Present study mainly aimed to evaluate 4a-u as G protein-coupled receptors (GPCR). In the mechanism, stimulation of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B) is a general reaction activated by a series of membrane-bound receptors such as GPCR. Protease-activated receptor-1 (PAR1) is a subfamily of related GPCR, which triggered by the division of fragment of its extracellular domain. Therefore, molecular docking is done to ensure the inhibition of PAR1 and PI3Kinase. PI3Kinase is a chief enzyme in the development of breast cancer via the Akt/mTOR pathway. Thus, in vitro PI3Kinase inhibition and anti-breast cancer studies has also done to screen medicinally important compounds among (4a-u). Based on the best binding affinity, in vitro relative % activity and IC50 values, compounds 4a, 4g, 4i, 4n, and 4u were screened for further preclinical studies in animal model evaluations.