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 this study new derivatives of O-[2-{''2-Substituted Aryl (''1,''3,''4 thiadiazolyl) ['3,'4-b]-'1,'2,'4- Triazolyl]-Ethyl]-p- chlorobenzald oxime (6-11)have been synthesized from the starting material p-chloro – E- benzaldoxime 1.Compound 2 was synthesized by the reaction of p-chloro – E- benzaldoxime with ethyl acrylate in basic medium. Refluxing compound 2 with hydrazine hydrate in ethanol absolute afforded 3. Derivative 4 was prepared by the reaction of 3 with carbon disulphide, treated of compound 4 with hydrazine hydrate gave 5. The derivatives (6-11) were prepared by the reaction of 5 with different substitutesof aromatic acids. The structures of these compounds were characterized from their melting points, infrared spectroscopy
... Show MoreThe work includes synthesis of 1,2,3-triazoles via click conditions and using the microwave irradiation starting from two synthesized azides: 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide (5) and perfluorobutylethyl azide (10) and different terminal alkynes. It also includes microwave enhanced synthesis of tetrazoles via the reaction of two synthesized azides i.e., perfluorobutylethyl azide (10) and 1,5-diazidopentane (13) with benzoyl cyanide. Most of the prepared compounds have been characterized by: TLC, FT-IR, 1H NMR, 13C NMR, LC-MS and microelemental analysis
sensor sampling rate (SSR) may be an effective and crucial field in networked control systems. Changing sensor sampling period after designing the networked control system is a critical matter for the stability of the system. In this article, a wireless networked control system with multi-rate sensor sampling is proposed to control the temperature of a multi-zone greenhouse. Here, a behavior based Mamdany fuzzy system is used in three approaches, first is to design the fuzzy temperature controller, second is to design a fuzzy gain selector and third is to design a fuzzy error handler. The main approach of the control system design is to control the input gain of the fuzzy temperature controller depending on the cur
... Show MoreThe aim of this paper is to design feed forward neural network to determine the effects of
cold pills and cascades from simulation the problem to system of first order initial value
problem. This problem is typical of the many models of the passage of medication throughout
the body. Designer model is an important part of the process by which dosage levels are set.
A critical factor is the need to keep the levels of medication high enough to be effective, but
not so high that they are dangerous.
Massive multiple-input multiple-output (MaMi) systems have attracted much research attention during the last few years. This is because MaMi systems are able to achieve a remarkable improvement in data rate and thus meet the immensely ongoing traffic demands required by the future wireless networks. To date, the downlink training sequence (DTS) for the frequency division duplex (FDD) MaMi communications systems have been designed based on the idealistic assumption of white noise environments. However, it is essential and more practical to consider the colored noise environments when designing an efficient DTS for channel estimation. To this end, this paper proposes a new DTS design by exploring the joint use of spatial channel and n
... Show MoreThe current research is concerned with studying the variables in the promotion process which influence the advertisement design structure, as the accomplished design and construction process is subject to many variables, whether they were intellectual or technological, internal or external variables. These variables may overlap in order to get a comprehensive system for the artistic configuration, that any design in its content reaches the highest levels of perfection is connected to the extent of its compliance with and approximation to these variables, that is why we find their reflections deeply rooted in the individual's mind, especially the designer artist who is influenced by everything surrounding him forming knowledge systems res
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