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 outstanding evidence of phthalimide pharmacophore in securing enhanced biological activities had encouraged further research and development into phthalimide-based derivatives as potential new drugs. In this study, phthalimide core was hybridized with aldehydes giving integrated imines displaying different types of functionalities and at alternating positions. The resulting compounds, therefore, provide an innovative window to explore possible differential biological effects as antioxidants and anticancer agents. A total of sixteen compounds were synthesized, and each was verified by FT-IR, H NMR, C NMR, and MS characterization. Herein, a facile single-step synthesis method was employed substituting the conventional two-step che
... Show MoreIn the present study, chitosan Schiff base has been prepared from chitosan reaction with p-chloro benzaldehyde. The AuNPs and AgNPs were manufactured by extract of onion peels as a reducing agent. The AuNPs and AgNPs that have been synthesized were characterized through UV-vis spectroscopy, XRD analyses and SEM microscopy. The polymer blends of the chitosan / PEG has been prepared by using the approach of solution casting. Chitosan Schiff base / PEG Au and Ag nanocomposites were synthesized, nanocomposites and polymer blends have been characterized by FTIR which confirm the formation of Schiff base by revealing a new band of absorption at 1693 cm-1 as a result of the (C=N) imine group. FESEM, DSC and TGA confirm the thermal stability
... Show MoreA novel Schiff base (SB) ligand, abbreviated as HDMPM, resulted from the condensation of 2-amino-4-phenyl-5-methyl thiazole and 4-(diethylamino)salicyaldehyde, and its metal complexes with [Co(II), Cu(II), Ni(II), and Zn(II)] ions in high yield were formed. The physico-chemical techniques such as elemental analysis, molar conductance, IR, 1H and 13C NMR, mass spectroscopy, and electronic absorption studies were utilized to characterize the synthesized compounds. The studied compounds were examined for their possible anticancer activity against a number of human cancerous cell lines, including A549 lung carcinoma, HepG2 liver cancer, HCT116 colorectal cancer, and MCF-7 breast cancer cell lines, with doxorubicin serving as the standard. The s
... Show MoreAbstract Organic compounds with pyrazole cores have a variety of uses, notably in the pharmaceutical and agrochemical sectors. The interest in creating pyrazole compounds, examining their many features, and looking for potential uses is growing. Our work has concert with synthesis of chalcones and pyrazolines, then finally pyrazoline-aniline derivatives and evaluation their anti-inflammatory, antibacterial and antifungal activities
A group of amine derivatives [4-aminobenzenesulfonamide derivatives, 2-aminopyridine and 2-aminothiazole] incorporated to α-carbon of diclofenac a well known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were designed and synthesized for evaluation as a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of the selected final compounds (9, 12 and 13) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (3 mg/Kg) of diclofenac sodium. All tested compounds produced a significant reduction in paw edema with respect to the effect of propylene glycol 50
... Show MoreThe preparation of a new Azo compounds of highly conjugated dimeric and polymeric liquid crystal to achieve the crystalline characteristics Which have structures assigned based on elemental analysis, IR 1HNMR and CHNS-O while mesogenic properties have been set for DSC and hot-stage polarizing optical microscopy. The compounds show enantiotropicnematic phase being displayed. The compounds show photoluminescence properties in the organic solution at room temperature, with the fluorescence band centered around 400 nm.
New substituted coumarins derivatives were synthesized by using nitration reaction to produce different nitro coumarin isomers which were separated from these isomers by using different solvent, and the reduction of nitro compounds was done to give corresponding amino coumarins. Temperature and reaction time of reaction were very important factors in determining the most productive nitro isotopes. A low temperature for three hours was sufficient to give a high product of a compound 6-nitro coumarin while increasing the temperature for a period of twenty-four hours that gave a high product of 8-nitro-coumarin. The synthesized compounds were confirmed by FT-IR,1 H-NMR, and13 C-NMR spectroscopy and all final compounds were tested for their ant
... Show MoreThis research discloses the synthesis of various polyester resins, the polyesters containing homoring aromatic and others heterocyclic were synthesized by the condensation polymerization of suitable monomers (which are containing variety function groups in different structures) with phthalic anhydride. The main objective is synthesis of new polyester with keeping a reasonable electrical insulating behavior. The structural of polymer was characterized by Fourier Transform infra-red spectroscopy FTIR and HNMR. The dielectric constant (real ε' and imaginary parts ε") and AC conductivity (σAC) for all the polyester samples are studied by varying the frequency (30, 50, 70, 90, 120, 300, 500Hz and 1KHZ) at 25⁰ C. Indeed, study of the electri
... Show MoreThis research included the preparation of 2-mercaptobenzoxazole (N1) by the reaction of ortho-aminophenol with carbon disulfide in an alcoholic potassium hydroxide solution. The 2-mercapto benzoxazole (N1) was then treated with hydrazine to obtain the 2-hydrazino benzoxazole (N2). A number of hydrazones (N3-N5) were prepared through the reaction of N2 with different benzaldehydes. The compound (N6) was also prepared whereby the ring closing of hydrazone (N3) using chloroacetylchloride, while the compound (N7) was prepared by treating 2-hydrazino benzoxazole with acetylacetone. When the compound (N1) was treated with formaldehyde, it afforded the compound (N8). Also, the N9 was obtained from the reaction of N1 with chloroacetic acid in th
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