Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design,Synthesis, and Anti-Proliferative Evaluation

This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound 8d was more potent than standard sorafenib. Such compound showed IC₅₀ values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC₅₀ values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound 8d also was found to exert exceptional VEGFR-2 inhibition activity with an IC₅₀ value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound 8h revealed excellent cytotoxic effects with IC₅₀ values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds 8a and 8e were found to inhibit VEGFR-2 kinase activity with IC₅₀ values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound 8d showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.     

Design,Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by ¹H-NMR, ¹³C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC₅₀ = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.     

A Review of Human Coronaviruses’ Receptors: The Host-Cell Targets for the Crown Bearing Viruses

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.     

Sintering of magnetoplumbite

A limiting density was reached at each sintering temperature. It was difficult to fix the operating mechanism during the initial stage of sintering. More than one mechanism overlap. At low temperatures surface diffusion predominates and at higher temperatures or firing periods a shift occurs to volume, then to grain boundary diffusion.During the intermetiate sintering stage, a straight line relationship was obtained on plotting the density or shrinkage against log time.The sintering rate was found to be inversely proportional to the particle size and increased in compositions deficit in iron oxide and at lower oxygen partial pressures.     

On chip chiral and plasmonic hybrid dimer or tetramer: Generic way to reverse longitudinal and lateral optical binding forces

For both the longitudinal binding force and the lateral binding force, a generic way of controlling the mutual attraction and repulsion (usually referred to as reversal of optical binding force) between chiral and plasmonic hybrid dimers or tetramers has not been reported so far. In this paper, by using a simple plane wave and an onchip configuration, we propose a possible generic way to control the binding force for such hybrid objects in both the near-field region and the far-field region. We also investigate different inter-particle distances while varying the wavelengths of light for each inter-particle distance throughout the investigations. First of all, for the case of longitudinal binding force, we find that chiral-plasmonic hybrid dimer pairs do not exhibit any reversal of optical binding force in the near-field region nor in the far-field region when the wavelength of light is varied in an air medium. However, when the same hybrid system of nanoparticles is placed over a plasmonic substrate, a possible chip, it is possible to achieve a reversal of the longitudinal optical binding force. Later, for the case of lateral optical binding force, we investigate a setup where we place the chiral and plasmonic tetramers on a plasmonic substrate by using two chiral nanoparticles and two plasmonic nanoparticles, with the setup illuminated by a circularly polarized plane wave. By applying the left-handed and the right-handed circular polarization state of light, we also observe the near-field and the far-field reversal of lateral optical binding force for both cases. As far as we know, so far, no work has been reported in the literature on the generic way of reversing the longitudinal optical binding force and the lateral optical binding force of such hybrid objects. Such a generic way of controlling optical binding forces can have important applications in different fields of science and technology in the near future.     

Theoretical characterisation of irreversible and reversible hydrogen storage reactions on Ni-doped C60 fullerene

An attempt has been made to characterise the irreversible and reversible hydrogen storage reactions on Ni-doped C₆₀ fullerene by using the state of the art density functional theory calculations. The single Ni atom prefers to bind at the bridge site between two hexagonal rings of C₆₀ fullerene, and can bind up to four hydrogen molecules with average adsorption energies of ?0.85, ?0.83, ?0.58, and ?0.31 eV per hydrogen molecule. No evidence for metal clustering in the ideal circumstances and the hydrogen storage capacity is expected to be as large as 8.9 wt%. While the desorption activation barriers of the complexes nH₂NiC₆₀ (n = 1, 2) are outside the desirable energy window recommended by the department of energy for practical applications (–0.2 to –0.6 eV), the desorption activation barriers of the complexes nH₂NiC₆₀ (n = 3, 4) are inside this window. The irreversible 2H₂ + NiC₆₀ and reversible 3H₂ + NiC₆₀ interactions are characterised in terms of several theoretical parameters such as: (1) densities of states and projected densities of states, (2) pairwise and non-pairwise additivity, (3) infrared, Raman, and proton magnetic resonance spectra, (4) electrophilicity, and (5) statistical thermodynamic stability.     

Hydrogen storage in SiC,GeC, and SnC nanocones functionalized with nickel,Density Functional Theory—Study

Hydrogen is regarded as one of the most potential sustainable energy sources in the future. Applications include transportation. Still, the event of materials for its storage is difficult notably as a fuel in vehicular transport. Nanocones are a promising hydrogen storage material. Silicon, germanium, and tin carbide nanocones have recently been proposed as promising hydrogen storage materials. In the present study, we have investigated the hydrogen storage capacity of $\mathrm{SiC},\mathrm{GeC},$ and $\mathrm{SnC}$ nanocones functionalized with Ni. The functionalized Ni atom are found to be adsorbed on $\text{SiCNC},\text{GeCNC},$ and $\text{SnCNC}$ with an adsorption energy of −5.56, −6.70, and −4.25 eV. The functionalized $\text{SiCNC},\text{GeCNC}$, and $\text{SnCNC}$ bind up to seven, six and four molecules of hydrogen with the adsorption energy of (−0.34, −0.35, and −0.26 eV) and an average desorption temperature of around 434, 447, and 332 K (ideal for fuel cell applications). The SiC, GeC, and SnC nanocones systems exhibit a maximum gravimetric storage capacity of 12.51, 7.78, and 4.08 wt%. We suggested that Ni SiCNC and Ni GeCNC systems can act as potential H₂ storage device materials because of their higher H₂ uptake capacity as well as their stronger interaction with adsorbed hydrogen molecules than Ni SnCNC systems. The hydrogen storage reactions are characterized in terms of the charge transfer, the partial density of states, the frontier orbital band gaps, and isosurface plots. And electrophilicity are calculated for the functionalized and hydrogenated $\mathrm{SiC},\mathrm{GeC},$ and $\mathrm{SnC}$ nanocones.