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.
Investigation of mesomorphic properties of new 1,3,4-thiadiazolines (which are synthesised via many steps in Scheme 1) was carried out in this study. These compounds are designed to have a heterocyclic unit, a carboxylate linkage group and a polar ether chain at the end of the molecule adjacent to the benzene ring, which enhance the dipolar interactions forces (varied from one to eight carbons) to investigate the association properties of their phases. The structure of the target compounds and the intermediates were confirmed by 1H NMR, 13C NMR, mass and FTIR spectral techniques. Polarised microscopic studies revealed that all the compounds in the series exhibited enantiotropic liquid crystalline properties. This was further confirmed using
... Show MoreBy condensation of benzaldehyde with thiourea in absolute ethanol in the presence of glacial acetic acid as a catalyst, the Schiff base(1-benzylidenethiourea)[I] was synthesized by synthesis of 4-(3-benzylidenethioureido)-4-thioxobut-2-enoic acid compound[II] by reaction of maleic anhydride with schiff base [I] in DMF. When treating compound [II] with ammonium persulfate (NH4)2S2O8 (APS) as an ethanol initiator to obtain polymer [III], compound [III] reacted to polymer [IV] with SOCl2 in benzene. Sulfamethizole, celecoxib, salbutamol, 4-aminoantipyrine to yield polymers [V-VIII], compound [IV] reaction with different drugs. Spectral evidence established the structure of synthesized co
Well integrity is a vital feature that should be upheld into the lifespan of the well, and one constituent of which casing, necessity to be capable to endure all the interior and outside loads. The casing, through its two basic essentials: casing design and casing depth adjustment, are fundamental to a unique wellbore that plays an important role in well integrity. Casing set depths are determined based on fracturing pressure and pore pressure in the well and can usually be obtained from well-specific information. Based on the analyzes using the improved techniques in this study, the following special proposition can be projected: The selection of the first class and materials must be done correctly and accurately in accordance with
... Show MoreWell integrity is a vital feature that should be upheld into the lifespan of the well, and one constituent of which casing, necessity to be capable to endure all the interior and outside loads. The casing, through its two basic essentials: casing design and casing depth adjustment, are fundamental to a unique wellbore that plays an important role in well integrity. Casing set depths are determined based on fracturing pressure and pore pressure in the well and can usually be obtained from well-specific information. Based on the analyzes using the improved techniques in this study, the following special proposition can be projected: The selection of the first class and materials must be done correctly and accurately in accordance with the
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Electrical magnate was designed and constructed, the optimum Magnetic flux and the effect of time on the physical properties of the alkaline (magnetic water) produced from the bottled drinking water [the total dissolved solids (TDS) or the electrical conductivity, and pH] were studied, to simulate ZamZam water in Mekka Saudi Arabia. Also, the efficiency of magnetic field from this designed electrical magnate in decreasing the TDS of sea water (of 1500 ppm NaCl Content), to convert it to water suitable for irrigation (TDS<1000 ppm) was investigated in this work.The results show that the magnetic flux from our designed electrical magnate in the range of (0.013- 0.08) Tesla and 30 minut
... Show MoreMethotrexate (MTX) is a folate antagonist widely used in the treatment of neoplastic diseases; its biotransformation in the liver produced active metabolites that promote hepatotoxicity. The present study was designed to evaluate the hepatoprotective effect of aqueous extract of Camellia sinensis (Green tea) against MTX-induced liver damage in rats. A model of liver injury in rats was induced by intraperitoneal injection of 20mg/kg MTX as a single dose followed by saline and 1.25% and 2.5% aqueous extract of green tea (GTE) were orally administered 7 days prior and 5 days after MTX-intoxication as a sole source of drinking water. After killing the animals, blood samples were obtained for evaluation of serum levels of alanine and
... Show MoreThe graphic privacy feature is one of the most important specifications for the existence of any type of design achievements alike, which is one of the graphic products with its multiple data, and from here the current research investigates the graphic privacy of vector graphics design with all its technical descriptions and concepts associated with it and the possibility of achieving it to the best that it should be from Where its formal structure in children's publications, where the structural structure of the current research came from the first chapter, which contained the research problem, which came according to the following question: What is the graphic privacy in the design of vector graphics in children's publ
... Show MoreActive vibration control is the main problem in different structure. Smart material like piezoelectric make a structure smart, adaptive and self-controlling so, they are effective in active vibration control. In this paper piezoelectric elements are used as sensors and actuators in flexible structures for sensing and actuating purposes, and to control the vibration of a cantilever beam by using sliding mode control. The sliding mode controller (SMC) is designed to attenuate the vibration induced by initial tip displacement which is equal to 15 mm. It is designed based on the balance realization reduction method where three states are selected for the reduced model from the 24th states that describe the c
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