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.
Schiff bases (Sh1-Sh3) have been synthesized (p-aminophenol) was condensed with different aromatic aldehyde in ethanol inthe presence of glacial acetic acid as catalyst. These Schiff bases on treatment with monochloroacetyl choride gave 3-chloro-1-(4-hydroxyphenyl)-4-(substituted)azetidin-2-one(Az4-Az6), with αmercaptoacetic acid gave 3-(4-hydroxyphenyl)-2-( substituted)thiazolidin-4-one (Th7-Th9) and with anthranilic acid gave 3-(4-hydroxyphenyl)-2(substituted)-2,3-dihydroquinazolin-4(1H)-one (Qu10-Qu12). The purity of the derivatives was confirmed by TLC. The some compoundsidentify by (FT-IR and1H, 13C-NMR) data. Some of derivatives were evaluated activity against several microbesto determine ability to inhibit bacterial in some h
... Show MoreIn this study, the effect of grafting with magnesium (Mg) ratios (0.1, 0.3, 0.5) on the structural and optical properties of cadmium oxide films (CdO) was studied, as these films were prepared on glass bases using the method of pulse laser deposition (PLD). The crystallization nature of the prepared membranes was examined by X-ray diffraction technique (XRD), which showed that the synthesis of the prepared membranes is polycrystalline, and (AFM) images also showed that the increased deformation with magnesium led to an increase in the grain size ratio and a decrease in surface roughness, as well as the absorption coefficient was calculated. And the optical energy gap for the prepared membranes, where it was found that the absorption coef
... Show MoreThis search include the synthesis of some new 1,3-oxazepine derivatives have been prepared, starting from reaction of L-ascorbic acid with dry acetone in presence of dry hydrogen chloride afforded the acetal (I). Treatment of the latter with p-nitrobenzoyl chloride in pyridine yielded the ester (II) which was dissolved in (65%) acetic acid in absolute ethanol yielded the glycol (III). The reaction of the glycol (III) with sodium periodate in distilled water at room temperature produced the aldehyde (IV). The compound (V) [4-(1,3-dioxoisoindolin-2-yl)benzoic acid] was synthesized by reaction p-aminobenzoic acid and phthalic anhydride in presence of (gla. CH3COOH). Reaction of compound (V) with thionyl chloride produced [4-(1,3-dioxoisoindoli
... Show MoreIn this study, the acid-alkaline transesterification of refined coconut seed oil (RCOSO) to fatty acid methyl ester was followed by the production of a trimethylolpropane-based thermosensitive biolubricant using potassium hydroxide, and its physicochemical characteristics were evaluated. The American Standard Test for Materials (ASTM) was employed to ascertain the biolubricant's pour point and index of viscosity, which were found to be -4 oC and 283.75, respectively. The opposite connection between lubricant viscosity and temperature was shown by the measured viscosities at varied transesterification to be transformed into biodiesel. Following this, a biolubricant was created by further transesterifiedtemperature. The ester gr
... Show MoreThe synthesis of new substituted cobalt Phthalocyanine (CoPc) was carried out using starting materials Naphthalene-1,4,5, tetracarbonic acid dianhydride (NDI) employing dry process method. Metal oxides (MO) alloy of (60%Ni3O4 40%-Co3O4 ) have been functionalized with multiwall carbon nanotubes (F-MWCNTs) to produce (F-MWCNTs/MO) nanocomposite (E2) and mixed with CoPc to yield (F-MWCNT/CoPc/MO) (E3). These composites were investigated using different analytical and spectrophotometric methods such as 1H-NMR (0-18 ppm), FTIR spectroscopy in the range of (400-4000cm-1), powder X-rays diffraction (PXRD, 2θ o = 10-80), Raman spectroscopy (0-4000 cm-1), and UV-Visib
... Show MoreMethotrxate (MTX) has become the standard of care and first-line therapy for patients who have RA and consider as a gold standard of treatment for RA. The role of MTX in the treatment of RA has now been well established. The use of MTX treatment of RA inhibits proliferation of the lymphocytes, reduces signs and symptoms this disease, reduces progression damage of the joints and improves quality of life outcome. Progranulin (PGRN) acts a role in autoimmune inflammatory, has important function in several processes including immune response. Present study has conducted to find the effect of MTX drugs as a therapeutic target for RA patients because of its ability to bind with tumor necrosis factor receptor (TNFR), with progranulin, obestatin an
... Show MoreA study worthy of study and objective analysis of the relationship of formal synthesis and innovative effectiveness in the design of modern women's fabrics, which deals with the first chapter the problem of research based on the following questions: (What role of innovative thinking in the formal synthesis of women's clothing designs Modern)
The research objectives included the following:
1 - defines the concept of innovative thinking and its effectiveness in design
2 - Reveal the role of innovative thinking in the formal synthesis of the designs of modern women's fabrics
The theoretical framework which included the following parts:.
1 - Innovative thinkin
... Show MoreAt the beginning of the twentieth century distorting handling totalitarian phenomena of art, which can be called the stage of the test, transition from the theory of ideal theory and other realistic is not cushy, since it requires vision and reading and other concepts, and in light of this dialectic manifested research problem by asking the following Is affected by the design idealism and realism. Through the above mentioned questions, the researcher found rationale for addressing this problem, the study through his research, which is marked (idealism and realism in a comparative study design). And demonstrated the importance of research in the identification of the concept and the effectiveness of the two theories idealism and realism a
... Show MorePolycyclicacetal was prepared from the reaction of PEG with aldehyde derived from Erythro-ascorbic acid (pentulosono-ɣ-lactone-2,3-enedianisoate).All these compounds were characterized by Thin Layer Chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR, 13CNMR, and mass spectra.The inhibitory effect of prepared polymer on the activity of human serum AcetylCholinesterase has been studied in vitro. The polymer showed a remarkable activity at low concentration (4.7x10-3 – 4.7x10-8M).