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.
By condensation of benzaldehyde with thiourea in absolute ethanol in the presence of glacial acetic acid as a catalyst, the Schiff base(1-benzylidenethiourea)[I] was synthesized by synthesis of 4-(3-benzylidenethioureido)-4-thioxobut-2-enoic acid compound[II] by reaction of maleic anhydride with schiff base [I] in DMF. When treating compound [II] with ammonium persulfate (NH4)2S2O8 (APS) as an ethanol initiator to obtain polymer [III], compound [III] reacted to polymer [IV] with SOCl2 in benzene. Sulfamethizole, celecoxib, salbutamol, 4-aminoantipyrine to yield polymers [V-VIII], compound [IV] reaction with different drugs. Spectral evidence established the structure of synthesized compounds: FTIR an
Investigation of mesomorphic properties of new 1,3,4-thiadiazolines (which are synthesised via many steps in Scheme 1) was carried out in this study. These compounds are designed to have a heterocyclic unit, a carboxylate linkage group and a polar ether chain at the end of the molecule adjacent to the benzene ring, which enhance the dipolar interactions forces (varied from one to eight carbons) to investigate the association properties of their phases. The structure of the target compounds and the intermediates were confirmed by 1H NMR, 13C NMR, mass and FTIR spectral techniques. Polarised microscopic studies revealed that all the compounds in the series exhibited enantiotropic liquid crystalline properties. This was further confirmed using
... Show MoreA new four series of 2,2′-([1,1′- phenyl or biphenyl]-4,4′-diylbis(azanediyl)) bis(N′-((E)-1-(4-alkoxyphenyl) ethylidene) acetohydrazide) [V-XI]a,b and 1,1′-(2,2′-([1,1′- phenyl or biphenyl]-4,4′-diyl bis(azanediyl)) bis- (acetyl)) bis(3-(4-ethoxyphenyl)-1H-pyrazole-4-carbalde hyde) [XII-XVIII]a,b have been synthesized by varying terminal lateral alkoxy chain length (n = 1–3, 5–8), central linkage group (phenyl or biphenyl) and induced pyrazole heterocyclic ring in the main chain. The last two series were synthesized by the cyclization of substituted acetophenone hydrazones with Vilsmeier–Haack reagent (DMF/POCl3) to produce 4-formylpyrazole derivatives. The chemical structures of the synthesized compounds were examine
... Show MoreObjective: The concentration-dependent nephroprotective effects of orally-administered aqueous green tea extract (AGTE) were studied. Materials and Methods: Forty rats of both sexes (weighing ٢٠٠-٢٥٠g) with various concentrations {٠.٦٢٥%, ١.٢٥% and ٢.٥% of aqueous green tea extract (AGTE)} as their main source of drinking fluid ٧ days before and ٥ days after administration of methotrexate (MTX). The parameters of oxidative stress, malondialdehyde (MDA) and reduced glutathione (GSH) were daily measured in kidney homogenate in addition to histopathological examinations after killing. Results: Analysis of data revealed significant amelioration of oxidative stress in groups of animals treated with different concentrations of AG
... Show MoreThe nephrotoxicity induced by methotrexate is a severe condition that greatly affects its therapeutic potential and has a significant inflammatory component. Fimasartan is an angiotensin receptor blocker that offers organ-protective effects and may be useful in mitigating renal injury. The present study explored the anti-inflammatory potential of two doses of fimasartan against methotrexate-mediated nephrotoxicity. Albino rats were intraperitoneally administered a single methotrexate (20 mg/kg). Intraperitoneal treatment with fimasartan (5 or 10 mg/kg/day) was initiated on day two after methotrexate injection and continued for seven consecutive days. Methotrexate significantly increased serum urea, creatinine, and NGAL concentrations. It al
... Show MoreMethotrexate is a folate antimetabolite chemical used to treat many forms of cancer and cleared mainly by kidney which result in a nephrotoxicity as a major complication of methotrexate. Trivalent chromium complex, chromium picolinate (CrPic), is mostly utilized to regulate glucose and raise insulin sensitivity—particularly in diabetes. The objective of this study was to assess the renoprotective effects of Chromium in mitigating nephrotoxicity induced by Methotrexate in rats. Study conducted on 32 male rats divided into 4 groups; Group I (Control group) in which rats received distilled water orally for 8 days, Group II (Induction group) which received a single intraperitoneal injection of Methotrexate (20 mg/kg) on
... Show MoreThe process of controlling a Flexible Joint Robot Manipulator (FJRM) requires additional sensors for measuring the state variables of flexible joints. Therefore, taking the elasticity into account adds a lot of complexity as all the additional sensors must be taken into account during the control process. This paper proposes a nonlinear observer that controls FJRM, without requiring equipment sensors for measuring the states. The nonlinear state equations are derived in detail for the FJRM where nonlinearity, of order three, is considered. The Takagi–Sugeno Fuzzy Model (T-SFM) technique is applied to linearize the FJRM system. The Luenberger observer is designed to estimate the unmeasured states using error correction. The develop
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