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.
The research deals with the analysis of the city's commercial center using geographic information systems to solve the problem of congestion by evaluating the efficiency and adequacy of car parking lots according to local and Arab standards. Undoubtedly, the importance of car parking areas, as they are not within the desired efficiency within the city, will lead to congestion and traffic becomes very difficult. Thus, the transportation service loses its most important characteristic, which is the ease of movement. Therefore, there has become an urgent need to study and analyze it, as well as to verify the adequacy of the service, and the amount of deficit required to be provided to solve the tra
... Show MoreThis paper describes a new proposed structure of the Proportional Integral Derivative (PID) controller based on modified Elman neural network for the DC-DC buck converter system which is used in battery operation of the portable devices. The Dolphin Echolocation Optimization (DEO) algorithm is considered as a perfect on-line tuning technique therefore, it was used for tuning and obtaining the parameters of the modified Elman neural-PID controller to avoid the local minimum problem during learning the proposed controller. Simulation results show that the best weight parameters of the proposed controller, which are taken from the DEO, lead to find the best action and unsaturated state that will stabilize the Buck converter system performan
... Show MoreA particle swarm optimization algorithm and neural network like self-tuning PID controller for CSTR system is presented. The scheme of the discrete-time PID control structure is based on neural network and tuned the parameters of the PID controller by using a particle swarm optimization PSO technique as a simple and fast training algorithm. The proposed method has advantage that it is not necessary to use a combined structure of identification and decision because it used PSO. Simulation results show the effectiveness of the proposed adaptive PID neural control algorithm in terms of minimum tracking error and smoothness control signal obtained for non-linear dynamical CSTR system.
The research dealt with the topic ' the aesthetics of design shape of interior spaces for the syndicate of physicians' as it reflects visions evolving to the level of tasting and positive interpretation for the space of work to be on a high design level.The research consisting of four chapters as follow; The first chapter examined the problem of the research contracted in the following question: Have the design shapes any role in achieving and showing the aesthetic side for the syndicate of physicians? so the goal of the research was showing the aesthetics of design shape of interior spaces for the syndicate of physicians, The chapter also included the objective spatial and temporal limits of research .Finally the terms were specified. T
... Show MoreHerein, the interfacial polymerization method has been used for the synthesis of PPy/NaVO3 composites with different compositions of NaVO3 (10 %, 20 %, 30 %, 40 % and 50 %) as an efficient electrode material for supercapacitors. The successful formation and composition of the as-prepared composites (PV1-PV5) were confirmed by FTIR, XRD, EDX, and SEM analysis. The electrochemical properties were investigated by cyclic voltammetry (CV), galvanometric charge–discharge measurement (GCD), and electrochemical impedance spectroscopy (EIS) in 0.5 M H2SO4 electrolyte. As compared to other, the PV4 composite exhibit excellent specific capacitance of 391 F g−1 at a current density of 0.75 A/g with good cycling stability of ∼59 % after 1000 cycle
... Show MoreA novel series of mixed-ligand complexes of the type, [ML1(L2)3]Clx [M= Cr(III), Fe(III), Co(II),Ni(II), Cu(II), Cd(II) and Hg(II), n = 2, 3], was synthesized using Schiff base (HL1) as main ligand, nicotinamide (L2) as secondary ligand, and the corresponding metal ions in 1:3:1 molar ratio. The main ligand, HL1 was prepared by the interaction of ampicillin drug and 4-chlorobenzophenone. The synthesized mixed ligand complexes were characterized by elemental analysis, UV-Vis, FT-IR,1H-NMR,13C-NMR and TG/DTG studies. In the mixed-ligand complexes, the Schiff base ligand, HL1 showed coordination to the central metal ion in tridentate manner via azomethine nitrogen, β-lactam ring oxygen and deprotonated carboxylic oxygen atoms, whereas the sec
... Show MoreThe prostaglandins inside inflamed tissues are produced by cyclooxygenase-2 (COX-2), making it an important target for improving anti-inflammatory medications over a long period. Adverse effects have been related to the traditional usage of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation, mainly centered around gastrointestinal (GI) complications. The current research involves the creation of a virtual library of innovative molecules showing similar drug properties via a structure-based drug design. A library that includes five novel derivatives of Diclofenac was designed. Subsequently, molecular docking through the Glide module and determining the binding free energy implementing the P
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