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.
Diacerein (DCN) is a semi-synthetic anthraquinone derivative of Rhein that is indicated for the management of osteoarthritis. Diacerein exhibits poor dissolution in the GIT fluids and suffers from low bioavailability upon oral administration in addition to the laxative effect of Rhein metabolites. The aim of the present study was to develop novasomal vesicles with optimized entrapment efficiency and size to serve as a carrier for transdermal delivery of diacerein. Novasomal vesicles were prepared by thin film hydration method thin film hydration. The prepared vesicles were optimized utilizing different surfactant to cholesterol molar ration, sonication type, different sonication times and varying fatty acid level. The prepared vesicles were
... Show MoreAbstract: Mixed ligand Mn(II), Co(II), Ni(II), Cu (II), Zn(II), and Cd(II) complexes with (TMAP) Schiff base ligand and (8HQ) have been composition and analyzed. Diagnosis by, melting point, solubility, Electronic, mass and IR-spectroscopic studies, conductivity elemental, thermoanalytical analysis displayed the forming of mononuclear complexes. Spectral studies results suggest an octahedral system or the metal (II) mixed complexes. The detainments of molar conductance of the mixed complexes in DMF coincide to electrolytic nature of the mixed complexes, consequently, these complexes could be subedited as [M(TMAP)(8Q)(H2O)]nX.yH2O (M=Co(II) and Cu(II) complexes(where n = 1, y = 0 ); [M(TMAP)(8Q)(H2O)]nX.yH2O (M = (where n = 1, y = 1 for Ni(
... Show MoreThe current study is unique in its emphasis on investigating design operation and concept from multiple scientific perspectives: including invention, technique, and design components. This research tends to study the methodology and creation of design process in a holistic manner so that the readers may grasp their characteristics and properties down to its minute epistemological detail. The investigation of the design concept is where the real groundwork and pressing need for the study begin. Creation and methodology are two primary concepts in relation to design these relationships can be formed in any design because of the various forces that act upon it. The primordial objective of this study is to evaluate the relationship betw
... Show MoreThere is a variety of artificial foot designs variable for use with prosthetic legs . Most of the design can be divided into two classes, articulated and non-articulated feet. one common non-articulated foot is the SACH . The solid ankle cushion heel foot referred to as the SACH foot has a rigid keel .
One key or the key factor in designing a new prosthesis is in the analysis of a patients response .
This view is the most important because if the foot does not provide functional , practical or cosmetically acceptable characteristics the patient will not feel comfortable with the prosthesis , therefore design and manufacturing a new foot is essential, this foot made from polyethylene, its different shape and characte
... Show MoreVariable-Length Subnet Masks (VLSM), often referred to as "subnetting a subnet", is used to maximize addressing efficiency. The network administrator is able to use a long mask on networks with few hosts, and a short mask on subnets with many hosts. This addressing scheme allows growth and does not involve wasting addresses. VLSM gives a way of subnetting a network with
minimal loses of IP addresses for a specific range. Unfortunately, the network administrator has to perform several mathematical steps (or use charts) to get the required results from VLSM. In this paper, a simple graph simulator is proposed (using Visual Basic 6.0 Language) to perform all the required mathematical steps and to display the obtained required informatio
This research includes theoretical and evaluation design of a polarizer filter of high transmission in the near IR region of (900-1200nm) for different incidence angles to obtain a long wave and short wave pass filter using analytical calculations. Results refer to a new configuration design in fewer layers than used in previous studies in the long wave pass at incidence angles (45o,50o,55o). Adopted Hafnium dioxide (HfO2) and Magnesium fluoride (MgF2) as coating material at design wavelength (933nm), the study also included design short wave pass polarizer by using the same coating material.
Variable-Length Subnet Masks (VLSM), often referred to as "subnetting a subnet", is used to maximize addressing efficiency. The network administrator is able to use a long mask on networks with few hosts, and a short mask on subnets with many hosts. This addressing scheme allows growth and does not involve wasting addresses. VLSM gives a way of subnetting a network with minimal loses of IP addresses for a specific range. Unfortunately, the network administrator has to perform several mathematical steps (or use charts) to get the required results from VLSM. In this paper, a simple graph simulator is proposed (using Visual Basic 6.0 Language) to perform all the required mathematical steps and to display the obtained required information (the
... Show MoreAn indoor spraying robot is built in this research to solve numerous challenges associated with manual spraying. The mechanical, hardware and essential technologies used are all detailed and designed. The proposed spraying robot's conceptual design is split into two parts: hardware and software. The mechanical design, manufacturing, electrical, and electronics systems are described in the hardware part, while the control of the robot is described in the software section. This robot's kinematic and dynamic models were developed using three links that move in the x, y, and z directions. The robot was then designed using SolidWorks software to compute each connection's deflection and maximum stresses. The characteristics of the stepper moto
... Show MoreDirectional control valves are designed to control direction of flow, while actuators maintain required speeds and precise positions. Magnetorheological (MR) fluid is a controllable fluid. Utilizing the MR fluid properties, direct interface between magnetic fields and fluid power is possible, without the need for mechanical moving parts like spools. This study proposes a design of a four-way three-position MR directional control valve, presents a method of building, and explains the working principle of the valve. An analysis of the design and finite elements using finite element method of magnetism (FEMM) software was performed on each valve. The magnetic circuit of the MR valve was analyzed and the performance was simulated. The
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