The spectrum of clinical efficacy of Methotrexate (MTX) is broad in that MTX is used in the treatment of certain cancers, severe psoriasis and rheumatoid arthritis.Various mechanisms by which cancer cells grown in tissue culture become resistant to anticancer drugs. The use of multiple drugs with different mechanisms of entry into cells and different cellular targets allows for effective chemotherapy and high cure rates. In an efforts to develop effective strategies that increase the therapeutic potential of anticancer drugs with less systemic toxicity ,are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. A promising approach to improve the cancer cell selectivity of methotrexate is the chemical transformation into reversible derivatives which convert the conjugate to the parent drug by virtue of enzyme within cancer tissue. The present study includes the synthesis of two derivatives of methotrexate which are :-Schiff base methotrexate-silibinin conjugate ( compound 5), and Methotrexate-silibinin conjugate (compound 6).The synthesis of the target compounds was accomplished following multistep reaction procedures. The chemical reactions were followed up and purity of the products was checked by TLC. The structures of the final compounds and their intermediates were characterized and identified by their melting points, infrared spectroscopy, 1H-NMR and elemental microanalysis(C H N S).The anticancer activity of these compounds was investigated by HEP-2 cell line(Larynx carcinoma), which showed that compounds 5 and 6 have the higher activity than methotrexate or silibinin alone.These are promising data for the discovery of new anticancer agents in future. These compounds may deliver the parent drug selectively into the cancer cells to be hydrolyzed by enzymes that are elevated in tumor tissues compared with normal tissues . Keywords: Methotrexate, Silibinin, Cancer treatment resistance, Folate receptor, Cancer cell targeting.
In order to promote sustainable steel-concrete composite structures, special shear connectors that can facilitate deconstruction are needed. A lockbolt demountable shear connector (LB-DSC), including a grout-filled steel tube embedded in the concrete slab and fastened to a geometrically compatible partial-thread bolt, which is bolted on the steel section's top flange of a composite beam, was proposed. The main drawback of previous similar demountable bolts is the sudden slip of the bolt inside its hole. This bolt has a locked conical seat lug that is secured inside a predrilled compatible counter-sunk hole in the steel section's flange to provide a non-slip bolt-flange connection. Deconstruction is achieved by demounting the tube from the t
... Show MoreIn the current worldwide health crisis produced by coronavirus disease (COVID-19), researchers and medical specialists began looking for new ways to tackle the epidemic. According to recent studies, Machine Learning (ML) has been effectively deployed in the health sector. Medical imaging sources (radiography and computed tomography) have aided in the development of artificial intelligence(AI) strategies to tackle the coronavirus outbreak. As a result, a classical machine learning approach for coronavirus detection from Computerized Tomography (CT) images was developed. In this study, the convolutional neural network (CNN) model for feature extraction and support vector machine (SVM) for the classification of axial
... Show MoreThis study designed to prepare ultrafine apixaban (APX) o/w nanoemulsion (NE) based gel with droplet size below 50 nm as a good method for transdermal APX delivery without using permeation enhancer, alternatively, the formulation components itself act as permeation enhancer. APX, a potent oral anticoagulant drug that selectively and directly inhibit coagulation factor Xa, was selected as a good candidate for transdermal delivery as it displays poor water solubility (0.028 mg/mL) and low bioavailability (50%). APX-NE gel was prepared using triacetin, triton-x-100 and carbitol as oil phase, surfactant and cosurfactant respectively, while Carbopol 940 used as a gelling agent. Ex vivo permeation of APX-NE gel through human stratum c
... Show MoreThe reservoir characterization and rock typing is a significant tool in performance and prediction of the reservoirs and understanding reservoir architecture, the present work is reservoir characterization and quality Analysis of Carbonate Rock-Types, Yamama carbonate reservoir within southern Iraq has been chosen. Yamama Formation has been affected by different digenesis processes, which impacted on the reservoir quality, where high positively affected were: dissolution and fractures have been improving porosity and permeability, and destructive affected were cementation and compaction, destroyed the porosity and permeability. Depositional reservoir rock types characterization has been identified de
Many designs have been suggested for unipolar magnetic lenses based on changing the width of the inner bore and fixing the other geometrical parameters of the lens to improve the performance of unipolar magnetic lenses. The investigation of a study of each design included the calculation of its axial magnetic field the magnetization of the lens in addition to the magnetic flux density using the Finite Element Method (FEM) the Magnetic Electron Lenses Operation (MELOP) program version 1 at three different values of current density (6,4,2 A/mm2). As a result, the clearest values and behaviors were obtained at current density (2 A/mm2). it was found that the best magnetizing properties, the high
... Show MoreThe reaction of 2-amino benzoic acid with 1,2-dichloroethane under reflux in methanol and KOH as a base to gave the precursor [H4L]. The precursor under reflux and drops of CH3COOH which reacted with (2mole) from salicycaldehyde in methanol to gave a new type N2O4 ligand [H2L], this ligand was reacted with (MCl2) Where [M= Co (II), Ni(II), Cu(II) and Zn(II)] in (1:1) ratio at reflux in methanol using KOH as a base, to give complexes of the general formula [M(L)]. All compounds have been characterized by spectroscopic methods [1H NMR ( just to the ligand), FTIR, uv-vis, atomic absorption], melting point, conductivity, chloride content, as well as magnetic susceptibility measurements. From the above data, the proposed molecular structu
... Show MoreThis work represents the preparation of the starting material, 3-chloro-2-oxo-1,4-dithiacyclohexane (S) using a new method. This material was reacted with, 4-phenylthiosemicarbazide to give (H3NS3) as a tetradentate ligand H3L. New complex of rhenium (V) with this ligand of the formula [ReO(L)] was prepared. New complexes of the general formula [M(HL)] of this ligand when reacted with some metal ions where: M = Ni(II), Cu(II), Cd(II), Zn(II), Hg(II) have been reported. The ligand and the complexes were characterized by infrared, ultraviolet–visible, mass, 1H nuclear magnetic resonance and atomic absorption spectroscopic techniques and by (HPLC), elemental analysis, and electrical conductivity. The proposed structure for H3L with Re (V) i
... Show MoreAddition chloro acetyl isothiocyanate (C3H2ClNOS) with 3-Aminoaceto phenone (C8H9NO) to prepare a fresh Ligand [N-(3-acetyl phenyl carbamothioyl)-2-chloroacetamide](L). The ligand (L) behaves as bidentate coordinating through O and S donor with metal ions, the general formula of all complexes [M(L)2(Cl)2](M+2 = Manganese(II), Cobalt(II), Cadmium(II) and Mercury(II)). Compounds were investigation by Proton-1, Carbon -13 NMR spectra (ligand (L) only), Element Microanalysis for C, N, H, O, S, Fourier-transform infrared, UV visible, Conductance
The reaction of 2-amino benzoic acid with 1,2-dichloroethane under reflux in methanol and KOH as a base to gave the precursor [H4L]. The precursor under reflux and drops of CH3COOH which reacted with (2mole) from salicycaldehyde in methanol to gave a new type N2O4 ligand [H2L], this ligand was reacted with (MCl2) Where [M= Co (II), Ni(II), Cu(II) and Zn(II)] in (1:1) ratio at reflux in methanol using KOH as a base, to give complexes of the general formula [M(L)]. All compounds have been characterized by spectroscopic methods [1H NMR ( just to the ligand), FTIR, uv-vis, atomic absorption], melting point, conductivity, chloride content, as well as m
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