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 complexes of the some trivalent transition metal ions of the uracil such as [M(Ura)3Cl3] and mixed ligand metal complexes with uracil and oxalic acid [M(Ura)2(OA)(OH2)Cl].H2O type, where (Ura)=Uracil, (OA= Oxalic acid dihydrate, (M= Cr+3 and Fe+3) were synthesized and characterized by the elemental analysis, FT.IR, electronic spectra, mass spectra and magnetic susceptibility as well as the conductivity measurements. Six–coordinated metal complexes were suggested for the isolated complexes of Cr+3 and Fe+3 with molecular formulas dependent on the nature of uracil and oxalic acid present. The proposed molecular structure for all complexes with their ions is octahedral geometries. The antibacterial efficiency was tested of metal salts, l
... Show MoreA polypyrrole‐graphene oxide (PPy/GO) nanocomposite was made chemically using a polymerization method in deep eutectic solvents made up of choline chloride and propionic acid in a 1:2 molar ratio. The purpose of this study is to examine the feasibility and efficacy of PPy/GO nanocomposite in the detection of metronidazole in pharmaceutical formulations utilizing spectrofluorometric techniques. Characterization of the synthesized PPy/GO nanocomposite was conducted using several methods such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier‐transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and X
Methotrexate (MTX), a folate antagonist agent, is mainly used in treatment of malignant tumors and autoimmune diseases. The present study was undertaken to determine whether antioxidant vitamin (vitamin A) could ameliorate methotrexate induced oxidative stress in male rabbits. Twenty male rabbits were randomly assigned into four groups. Group 1: control group, Group 2: MTX-treated group (received 20 mg/kg MTX intraperitoneally), Group 3: Vit.A treated group received 5000 IU Vit.A orally) and Group 4: MTX+Vit.A treated group received MTX 20 mg/kg plus 5000 IU vit.A). After 4 weeks of treatment, blood samples were collected by cardiac puncture to determine the serum malondialdehyde (MDA), as a good indicator for lipid peroxidation and
... Show MoreBackground: Methotrexate (MTX) was one of the first drugs synthesized for a specific chemotherapeutic purpose used to inhibit folic acid (FA) for the treatment of acute lymphoblastic leukemia in children. Its history is closely related to the discovery and characterization of folic acid. It is used clinically in medicine to treat a range of cancerous and noncancerous conditions. MTX is currently used in gynecology to treat disorders arising from trophoblastic tissue, namely, ectopic pregnancy. MTX, the most frequently used diseasemodifying anti-rheumatic drug (DMARD), suppresses disease activity and reduces joint damage. The aim of study: It is designed to demonstrate the effect of MTX (7.5 mg/wk.) on the histogenesis of gonad (testis) of n
... Show MoreBoth methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and histopathological studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group
... Show MoreBoth methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and histopathological studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group VII) vit
... Show MoreDrug-induced acute kidney injury is a serious disorder. Oxidative stress has a key role in its initiation and progression. In this study, the possible ameliorative effect of fimasartan against methotrexate-induced nephrotoxicity was investigated in comparison with α-tocopherol in rats. Wistar rats were allocated into six groups and treated as follows: group Ӏ received water on a daily basis for 8 successive days; group ӀӀ received methotrexate (20 mg/kg) on day 1, followed by water for 7 successive days; group ӀӀӀ received fimasartan (3 mg/kg/day) for 7 successive days; group IV received α-tocopherol (1 g/kg/day) for 7 successive days; group V re
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