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.
New 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 MoreNine new compounds of 2-amino-5-chlorobenzothiazole derivatives were synthesized. These new compounds were formed through the reaction of 2-amino-5-chlorobenzothiazole 1 with ethyl chloroacetate and KOH, which gave an ester derivative 2, followed by refluxing compound 2 with hydrazine hydrate to afford hydrazide derivative 3. The reaction of compound 3 with CS2 and KOH gave 1,3,4-oxadiazole-2-thiol derivative 4, and then the reaction of compound 2 with thiosemicarbazide to produce compound 5 then treated it with 4%NaOH led to ring closure to provide 1,2,4-triazole-3-thiol derivative
... Show More4-Amino-N-(5-methyl-isaxazol-3-yl)-benzenesulfonamide was synthesized by reacting the diazonium salt of sulfamethoxazole with 3-amino phenol. Complexes of Ni(II), Pd(II), Au(III), and Pt(IV) were produced and characterized by atomic absorption, elemental microanalysis, infrared spectroscopy, liquid chromatography–mass spectroscopy, thermogravimetric analysis, different scanning calorimetry, and ultraviolet–visible spectroscopy. Furthermore, the conductivity and magnetic properties were quantified. According to the analytical studies, all complexes were found to possess a 1:2 metal–ligand ratio and were non-electrolytes, except the Au(III) complex electrolyte, which had a 1:1 metal:ligand ratio. The biological activities of some of the
... Show MoreIn this work, new compounds containing 1,2,4-oxadiazole units were synthesized, characterized, and their crystalline liquid qualities were also studied. The synthesis of compound [I ] starts with the reaction 4-hydroxybenzonitrile with phthaloyl chloride to yield nitrile compound. Then the later compound reacted with hydroxyl amine hydrochloride to obtain compound [II]. Next, 1,2,4-Oxadiazole compounds [III]a-c and [IV] were obtained by the reaction between compound [II] with various acid chlorides(acetyl chloride, chloroacetyl chloride, benzoyl chloride) and phthaloyl chloride in pyridine, respectively. FTIR, 1HNMR and mass spectroscopy were used to analyze the synthesized compounds Spectroscopic investigation verified the synthetic
... Show MoreThe study involved the synthesis of new complexes with tetradentate ligand (LH). The general formula of complexes was [M(LH)(H2O)2] with M of Ni2+, Co2+, Cu2+, and Zn+. The ligand was synthesized by treating the 2-hydroxybenzohydrazide with salicylaldehyde. The structural characteristics of ligands and complexes were analyzed using various techniques, including elemental analyses, magnetic susceptibility, molar conductivity, infrared, ultraviolet absorption, mass, and NMR spectroscopy studies. The physical measurements indicated that the prepared complexes are non-electrolyte and showed that the ligand is tetradentate when coordinated with metal ions through the nitrogen of azomethine (–C=N–), two oxygen atoms of O–H phenolic,
... Show MoreThe operating characteristics of optoelectronic devices depend critically on the properties physical of the constituent materials, interesting compound has been focused on this research formed from group III and V of the periodic table. Thin film n-InSb heterjuntion were successfully fabricated on p-Si substrates by thermal evaporation technique at different annealing temperature (as prepared, 400,500,600) °C. The effect of annealing temperature on the structural, surface morphology, optical and optoelectronic properties of InSb films were investigated and studied. The crystal structure of the film was characterized by X-ray diffraction and techniques. AFM techniques inspect the surface morphology of InSb films, the study presented the val
... Show MorePorous Silicon (PS) layer has been prepared from p-type silicon by electrochemical etching method. The morphology properties of PS samples that prepared with different current density has been study using atom force measurement (AFM) and it show that the Layer of pore has sponge like stricture and the average pore diameter of PS layer increase with etching current density increase .The x-ray diffraction (XRD) pattern indicated the nanocrystaline of the sample. Reflectivity of the sample surface is decrease when etching current density increases because of porosity increase on surface of sample. The photolumenses (PL) intensity increase with increase etching current density. The PL is affected by relative humidity (RH) level so we can use
... Show MoreLetrozole (LZL) is a non-steroidal competitive aromatase enzyme system inhibitor. The aim of this study is to improve the permeation of LZL through the skin by preparing as nanoemulsion using various numbers of oils, surfactants and co-surfactant with deionized water. Based on solubility studies, mixtures of oleic acid oil and tween 80/ transcutol p as surfactant/co-surfactant (Smix) in different percentages were used to prepare nanoemulsions (NS). Therefore, 9 formulae of (o/w) LZL NS were formulated, then pseudo-ternary phase diagram was used as a useful tool to evaluate the NS domain at Smix ratios: 1:1, 2:1 and 3:1.