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.
This study involved the effect of anew nickel (II) complexs with formla [NiL2(H2O)2].2.5ETOH where L=Bis[5-(p-nitrophenyL)-4-phenyL-1,2,4-traizole-3-dithocarbamato hydrazide] diaqua. nickel(II). Ethanol(2.5).and anti-cancer drug cyclophosphamide on specific actifity of two Liver enzymes (GOT,GPT) in the (Liver,kidney) tissues and on the creatinine Level in the kidney byUtilizing an invivosystem in femalmice.The result showed that inhibition in the activity of GPT and GOT enzymes in theLiver and in both nickel (II) complex and cyclophosphamide drug (CP) . mice weretreated with three doses (90,180,320) µg/mouse for three days for each group.The Liver show's the highest rate of GPT inhibition was about 97.43% at180µg/mouse regarding the ki
... Show MoreThe design of future will still be the most confusing and puzzling issue and misgivings that arouse worry and leading to the spirit of adventures to make progress and arrive at the ways of reviving, creativity and modernism. The idea of prevailing of a certain culture or certain product in design depends on the given and available techniques, due to the fact that the computer and their artistic techniques become very important and vital to reinforce the image in the design. Thus, it is very necessary to link between these techniques and suitable way to reform the mentality by which the design will be reformed, from what has been said, (there has no utilization for the whole modern and available graphic techniques in the design proce
... Show MoreI've been in this research preparation and diagnostic complexes mixed Kandat of Alcavaúan Alpiculan ion Althaaossianat with some metal ions has been reactive in ethanol solvent and distilled water by (1:1) and water complexes and lotions to the accounts of the metal in the complex
In this research a computational simulation has been carried out on the design and properties of the electrostatic mirror and a mathematical expression has been suggested to represent the axial potential of an electrostatic mirror. The electron beam path using the Bimurzaev technique had been investigated as mirror trajectory with the aid of Runge – Kutta method. The spherical and chromatic aberration coefficients of mirror has computed and normalized in terms of the focal length. The choice of the mirror depends on the operational requirements. The Electrode shape of mirror two electrodes has been determined by using package SIMION computer program. Computations have shown that the suggested potentials giv
... Show MoreThis paper is concerned with preliminary test single stage shrinkage estimators for the mean (q) of normal distribution with known variance s2 when a prior estimate (q0) of the actule value (q) is available, using specifying shrinkage weight factor y( ) as well as pre-test region (R). Expressions for the Bias, Mean Squared Error [MSE( )] and Relative Efficiency [R.Eff.( )] of proposed estimators are derived. Numerical results and conclusions are drawn about selection different constants including in these expressions. Comparisons between suggested estimators with respect to usual estimators in the sense of Relative Efficiency are given. Furthermore, comparisons with the earlier existi
... Show MoreBall and Plate (B&P) system is a benchmark system in the control engineering field that has been used to verify many control methods. In this paper the design of a sliding mode . controller has been investigated and verified in real-time via implementation on a real ball and plate system hardware. The mathematical model has been derived and the necessary parameters have been measured. The sliding mode controller has been designed based on the obtained mathematical model. The resulting controller has been implemented using the Arduino Mega 2560 and a ball and plate system built completely from scratch. The Arduino has been programmed by the Arduino support target for Simulink. Three test signals has been used for verification purposes
... Show MoreNew Schiff bases derivatives [IV]a-e is prepared via condensation of Derythroascorbic acid with p-substituted aldehydes in dry benzene. To obtain these derivatives, the 5,6-O-isopropylidene-L-ascorbic acid[I] was chosen as starting material, compound prepared from the reaction of L-ascorbic acid as starting material. Compound[I] was prepared from the reaction of L-ascorbic acid with dry acetone in the presence of hydrogen chloride. The esterification of hydroxyl groups at C-2 and C-3 positions with excess ofethyl α –chloroacetate in the presence of sodium acetate produce acorresebonding ester [II] , which was condensed with hydrazine hydrate to give new hydrazide [III] . The new Schiff bases [IV]a-e were synthesized by reaction of acid h
... Show MoreSolvent- free thermal heating, one-pot condensation of acetophenone, ethyl cyanoacetate or malononitrle and substituted Aromatic aldehyde, ammonium acetate give, 2oxo-3-cyano-4-substituted Aryl-6-phenyl pyridine [I]a-h , or 2-amino-3-cyano-4-substituted Aryl-6-phenyl pyridine derivatives[II]a-f , respectively. Treatment of compounds 2-oxo-3-cyano-4-substituted Aryl-6-phenyl pyridine with phosphorous penta sulphide (P2S5), give 2-thioxo-3-cyano-4-substituted Aryl-6-phenyl pyridine derivatives[III]a-c . All prepared compounds
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