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 new Schiff base 1‐[(2‐{1‐[(dicyclohexylamino)‐methyl]‐1H‐indol‐3‐yl}‐ethylimino)‐methyl]naphthalen‐2‐ol (HL) was prepared from 1‐{[2‐(1H‐Indol‐3‐yl)‐ethylimino] methyl}‐naphthalen‐2‐ol and dicyclohexyl amine. From this Schiff base, monomeric complexes [M (L)n (H2O)2 Cl2] with M = Cr, Fe, Mn, Cd, and Hg were synthesized and characterized based on elemental analysis (EA), FT‐IR, mass(MS), UV‐visible, thermal analysis, magnetic moment, and molar conductance. The results showed that the geometrical structural were octahedral geometries for the Cr(III) and Fe(III) complex
In this article, new Schiff base ligand LH-prepared Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II), Pd(II), and Pt(II) materials were analyzed using spectroscopy (1 Metal: 2 LH). The ligand was identified using techniques such as FTIR, UV-vis, 1H-13C-NMR, and mass spectra, and their complexes were identified using CHN microanalysis, UV-vis and FTIR spectral studies, atomic absorption, chloride content, molar conductivity measurements, and magnetic susceptibility. According to the measurements, the ligand was bound to the divalent metal ions as a bidentate through oxygen and nitrogen atoms. The complexes that were created had microbicide activity against two different bacterial species and one type of fungus. DPPH techniques were bei
... Show MoreA new nano-sized NiMo/TiO2-γ-Al2O3 was prepared as a Hydrodesulphurization catalyst for Iraqi gas oil with sulfur content of 8980 ppm, supplied from Al-Dura Refinery. Sol-gel method was used to prepare TiO2- γ-Al2O3 nano catalyst support with 64% TiO2, 32% Al2O3, Ni-Mo/TiO-γ-Al2O3 catalyst was prepared under vacuum impregnation conditions to loading metals with percentage 3.8 wt.% and 14 wt.% for nickel and molybdenum respectively while the percentage for alumina, and titanium became 21.7, and 58.61 respectively. The synthesized TiO2- γ-Al2O3 nanocomposites and Ni-Mo /TiO2
... Show MoreHistone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed inhibition of growth of human colon adenoc
... Show MoreTwo compounds,[2-amino-4-(4-nitro phenyl) 1,3-thiazole],(4) and [2-amino-4-(4-bromo phenyl) 1,3-thiazole],(5), were synthesized by refluxing thiourea (1) with each of para-ntiro and para-bomophanacyl bromides(2) and (3) respectively, in absolute methanol. Then, by reaction of [5] with 3,5-dinitrobenzoyl chloride in dimethylformamide (DMF) yielded (6) .On the other hand, reaction of (4) with chloroacetyl chloride in dry benzene afforded (7), which is upon treatment with thiourea in absolute methanol, af
... Show MoreAll new compounds synthesized by many reactions starting from a product the compounds [I]a,b from reaction of 3-phenylenediamine or 4-phenylenediamine with chloroacetyl chloride, then the compounds [I]a,b reacted with potassium thiocyanate to yield compounds [II]a,b. While the compounds[III]a,b yield from reacted the compounds [I]a,b with sodium azide then the compounds [III]a,b reacted 1,3-dipolar cycloaddition reaction with acrylic acid to give compounds [IV]a,b and the later compounds reacted with phenylene diamine to product benzimidazole compounds [V]a,b . In addition to synthesized acid chloride compounds [VI]a,b by reacted the compounds [IV]a,b with thionyl chloride .Finally reacted the compounds [VI]a,b with different aromatic amine
... Show MoreA novel series of liquid crystalline compounds containing 2,4-thiazolidinedione units with varying terminal alkyl chain lengths was successfully synthesized and characterized. The chemical structures of the synthesized compounds were confirmed by FT-IR, ¹H-NMR, and mass spectrometry. The mesomorphic behavior was investigated using polarized optical microscopy (POM) and differential scanning calorimetry (DSC). Compounds [V]₄, [V]₅, and [V]₆ exhibited enantiotropic nematic phases, while compound [V]₈ displayed a smectic A (SmA) phase. No liquid crystalline behavior was observed for compound [V]₃. The liquid crystalline properties were found to depend on the terminal-to-lateral chain length ratio, molecular geometry, and the nature
... Show MoreRecently, some prostate cancer patients have acquired resistance to the second -generation drugs (anzalutamide and apalutamide) prescribed for the treatment of this disease due to the emergence of the F876L mutation, which represents a challenge to modern medicine. In this study, a new series of 2-thiohydantoin derivatives were prepared through the reaction of different derivatives of maleimide (1c-4c) with isothiocyanate derivatives. The prepared compounds were diagnosed using FT-IR,1H-NMR ,13C-NMR, Mass spectra. The prepared series compounds has been studied against prostate cancer cells. The MTT assay was used to determine the activity of the prepared compounds against prostate cancer cells. The da
... Show MorePrevious reports demonstrated the effectiveness of silibinin hemisuccinate as a potential intraocular pressure-lowering agent. The exact mechanism by which silibinin exerted this effect has not yet been documented, but might suggested to interfere with aqueous humor formation. The present study was designed to evaluate the comparative efficacy of silibinin as IOP lowering agent to that of betaxolol in normotensive rabbits, and the interaction of silibinin with betaxolol as a way for investigating the possible mechanism of action of silibinin in this respect. The effects of instillation of 0.75% silibinin solution and 0.5% betaxolol eye drops in the eyes of normotensive rabbits were evaluated using indentation tonometry. The results showe
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