The preparation of 4,5-dihydro-2H-benz[e]indazoles from dilithiated 2-tetralone phenylhydrazone and aromatic esters

The phenylhydrazone of 2-tetralone was dilithiated with excess lithium diisopropylamide followed by condensation with several aromatic esters, and the resulting intermediates were acid cyclized to 4,5-dihydro-2H-benz[e]indazoles.     

An Investigation of ~4He+~(12)C and ~4He+~(16)O Reactions Using the Cluster Model

The α-target semimicroscopic single folding potentials have been derived by folding a composite (repul-sive and attractive) effective α-α interaction with the α-cluster distribution density in the target nuclei. The obtained potentials are considered as the real part of the nuclear optical model potentials, while the imaginary parts are phe-nomenologicaly expressed using the Woods-Saxon form. Nine sets of measured experimental data of the 4He+12C and 4 He+16O elastic rainbow scattering over the energy range 80-240 MeV are analyzed using the obtained potentials. The data are successfully reproduced using the extracted potentials. The resulted reaction cross sections are also investigated and compared with the available corresponding data.     

Analysis of <Superscript>4</Superscript>He+<Superscript>40</Superscript>Ca and <Superscript>4</Superscript>He+<Superscript>44</Superscript>Ti scattering using different optical model potentials

Elastic scattering of ⁴He+⁴⁰Ca and ⁴He+⁴⁴Ti reactions at backward angles has been analyzed using two differentmodels, microscopic and semimicroscopic folding potentials. The derived real potentials supplemented with phenomenological Woods–Saxon imaginary potentials, provide good agreement with the experimental data at energy E_c.m. = 21.8 MeV without need to renormalize the potentials. Coupledchannels calculations are used to extract the inelastic scattering cross section to the low-lying state 2+ (1.083 MeV) of ⁴⁴Ti. The deformation length is obtained and compared with the electromagnetic measurement values as well as those obtained from previous studies.     

Rhodium catalysed dehydrogenative borylation of alkenes: vinylboronates via C-H activation

We present herein a high yield, highly selective catalytic synthesis of vinylboronate esters (VBEs), including 1,1-disubstituted VBEs, from alkenes without significant hydrogenation or hydroboration, using the simple catalyst precursor, trans-[RhCl(CO)(PPh3)2] (1), and the diboron reagents B2pin2 (2a, pin = pinacolato = OCMe2CMe2O) or B2neop2 (2b, neop = neopentylglycolato = OCH2CMe2CH2O), or the monoboron reagent HBpin, all of which are commercially available. The reactions were conducted at 80 degrees C using conventional heating, or in a microwave reactor at 150 degrees C.     

Design,Synthesis, In Silico and In Vitro Studies of New Immunomodulatory Anticancer Nicotinamide Derivatives Targeting VEGFR-2

VEGFR-2, the subtype receptor tyrosine kinase (RTK) responsible for angiogenesis, is expressed in various cancer cells. Thus, VEGFER-2 inhibition is an efficient approach for the discovery of new anticancer agents. Accordingly, a new set of nicotinamide derivatives were designed and synthesized to be VEGFR-2 inhibitors. The chemical structures were confirmed using IR, ¹H-NMR, and ¹³C-NMR spectroscopy. The obtained compounds were examined for their anti-proliferative activities against the human cancer cell lines (HCT-116 and HepG2). VEGFR-2 inhibitory activities were determined for the titled compounds. Compound 8 exhibited the strongest anti-proliferative activities with IC₅₀ values of 5.4 and 7.1 µM against HCT-116 and HepG2, respectively. Interestingly, compound 8 was the most potent VEGFR-2 inhibitor with an IC₅₀ value of 77.02 nM (compare to sorafenib: IC₅₀ = 53.65 nM). Treatment of HCT-116 cells with compound 8 produced arrest of the cell cycle at the G0–G1 phase and a total apoptosis increase from 3.05 to 19.82%—6.5-fold in comparison to the negative control. In addition, compound 8 caused significant increases in the expression levels of caspase-8 (9.4-fold) and Bax (9.2-fold), and a significant decrease in the Bcl-2 expression level (3-fold). The effects of compound 8 on the levels of the immunomodulatory proteins (TNF-α and IL-6) were examined. There was a marked decrease in the level of TNF-α (92.37%) compared to the control (82.47%) and a non-significant reduction in the level of IL-6. In silico docking, molecular dynamics simulations, and MM-PBSA studies revealed the high affinity, the correct binding, and the optimum dynamics of compound 8 inside the active site of VEGFR-2. Finally, in silico ADMET and toxicity studies indicated acceptable values of drug-likeness. In conclusion, compound 8 has emerged as a promising anti-proliferative agent targeting VEGFR-2 with significant apoptotic and immunomodulatory effects.     

A Runge–Kutta type four-step method with vanished phase-lag and its first and second derivatives for each level for the numerical integration of the Schrödinger equation

The investigation of the impact of the vanishing of the phase-lag and its first and second derivatives on the efficiency of a four-step Runge–Kutta type method of sixth algebraic order is presented in this paper. Based on the above mentioned investigation, a Runge–Kutta type of two level four-step method of sixth algebraic order is produced. The error and the stability of the new obtained method are also studied in the present paper. The obtained new method is applied to the resonance problem of the Schrödinger equation the efficiency of the method to be examined.     

A novel biosensor for early diagnosis of liver cancer cases using smart nano‐magnetic metal–organic framework

For the first time, alpha‐fetoprotein (AFP) quantification as an early test for liver cancer diagnosis competing with other interfering analytes and factors based on a novel nano‐magnetic metal–organic framework (MOF) was investigated. The novel nano‐magnetic MOF was synthesized via a simple preparation method, and characterized using various techniques. The X‐ray photoelectron spectrum of the nano‐magnetic MOF shows Cu 2p, O 1s, N 1s and C 1s peaks that evidence the presence of these elements in the sample without any impurities. Scanning and transmission electron microscopy images show the nano‐magnetic MOF with average size between 22 and 43 nm. The results of a photoluminescence study show that the nano‐magnetic MOF exhibits strong emission at 418 nm after excitation at 354 nm. Moreover, a Stern–Völmer graph shows a linear calibration curve over an AFP concentration range 1.0–520 ng ml^?1 with a correlation coefficient of 0.997, detection limit of 1.18 ng ml^?1 and quantitation limit of 3.58 ng ml^?1. According to the marked quenching of the photoluminescence intensity of the nano‐magnetic MOF using various concentrations of AFP, it was successfully used as a biosensor for AFP in serum samples collected from hepatitis patients in addition to healthy males and females. The quenching mechanism was well studied, and found to be a dynamic type. The present work offers a simple, low‐cost, room‐temperature and rapid technique, being non‐time‐consuming, highly accurate, selective and highly sensitive compared with most published methods.     

Discovery of New VEGFR-2 Inhibitors: Design,Synthesis, Anti-Proliferative Evaluation,Docking, and MD Simulation Studies

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC₅₀ values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC₅₀ of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.     

Dough Performance and Quality Evaluation of Cookies Prepared from Flour Blends Containing Cactus (Opuntia ficus-indica) and Acacia (Acacia seyal) Gums

Acacia (AG) and cactus gums (CG) were mixed into wheat flour at the 3% and 6% levels. The flour blends were tested for their pasting, dough development, and extensibility behaviors. The blends were used to make cookies, which were then evaluated for their physical, textural, and sensory qualities. Both types of gum reduced the setback viscosities, water absorption, and farinograph quality numbers while increasing the water retention capacity, dough development time, and extensibility. The thickness and diameter of the cookies decreased in the presence of the cactus gum, while the acacia gum resulted in greater thickness and diameter. The addition of more gums increased the hardness of the cookies while decreasing their fracturability. All the cookie types were acceptable for all the sensory attributes studied. When compared to the control, the panelists preferred the color of the cookies with a higher level of gum. Overall, the presence of gums in the formulation resulted in the development of cookies with improved technological and sensory attributes. Likewise, the cookies with higher levels of gum can deliver 6% more soluble fiber without compromising their overall acceptability.