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 reaction of methyldopa with o-vanillin in refluxing ethanol afforded Schiff base and characterized through physical analysis with a number of spectra also the study of biological activity. The geometry of the Schiff base was identified through using (C.H.N) analysis, Mass, 1H-NMR, FT-IR, UV-Vis spectroscopy. Metal complexes of Cr3+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Hg2+ with Schiff base have been prepared in the molar ratio 2:1 (Metal:L), (L = Schiff base ligand) except Hg2+ at molar ratio 1:1 (Hg:L). The prepared complexes were characterized by using Mass, FT-IR and UV-Vis spectral studies, on other than magnetic properties and flame atomic absorption, conductivity measurements. According to the results a dinuclear octahedral geo
... Show MoreThe purpose of this study is to underline the progression and development of research regarding oxygen-containing heterocycles as well as the contribution that some oxygen-containing heterocycles have made as anticancer medicines. A series of publications about the antitumor effects of derivatives of heterocyclic compounds containing an oxygen atom, such as furan, benzofuran, oxazole, benzoxazole, and oxadiazole, were evaluated, and their anticancer activities showed encouraging results when compared to those of established standard treatments.
Rheumatoid arthritis is an autoimmune diseasecharacterized by chronic inflammationthat affects joints and cartilage. Bone complications such asRA-relatedosteoporosis are one of the most extra-articular manifestations. Many inflammatory mediators are released during RA disease pathophysiology; these mediators stimulate osteoclast genesis of bone by direct effects on RANKL and OPG. The study aimedto measure RANKL, OPG in RA patients treated with Etanercept only and other groups treated with Methotrexate onlyat baseline and after three months to evaluate bone state. An observational case-control prospective study was done on 30 RA patients who received MTX, 30 RA patients who received ETN, and 30 healthy,age-matched control groups. The
... Show MoreSecnidazole was linked with ciprofloxacin as mutual prodrugs to get antibiotics with broader spectrum of activity, improved physicochemical properties and given by single dose to improve patient’s compliance. Furthermore, they provide structural modifications to overcome bacterial adaptation. The structures of the synthesized compounds were confirmed using FT-IR, mass spectrometry, elemental microanalysis (CHNO) and some physiochemical properties. This modification was led to an increase in Log P values for Mutual I (Log P 1.114) and Mutual II (Log P 1.97) compared with its values for Secnidazole (Log P -0.373) and ciprofloxacin (Log P -0.832). The solubility of prodrugs had been determined in different media, Mutual II showed 1
... 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 MoreMost pathological effects of lead on the body are due to ability of lead to bind with important cellular molecules of various tissues and organs leading to formation abnormal molecules and thus to emergence of pathological conditions. To evaluation the risk to the health status of Iraqi workers who work in the batteries industry, expression of three types of calmodulin related genes were examined. Blood samples were collected from worker working in Iraqi industry of batteries (located in Al-Waziriya), then RNAs extraction were done thereby gene expression for Calcium/Calmodulin- dependent protein kinase2 (CaMKK2), C-X-C Chemokine receptor 4 (CXCR4) and mitogen activated protein kinase kinase 6 (MAP2K6) was done for each sample by using RT-q
... Show MoreThe physical substance at high energy level with specific circumstances; tend to behave harsh and complicated, meanwhile, sustaining equilibrium or non-equilibrium thermodynamic of the system. Measurement of the temperature by ordinary techniques in these cases is not applicable at all. Likewise, there is a need to apply mathematical models in numerous critical applications to measure the temperature accurately at an atomic level of the matter. Those mathematical models follow statistical rules with different distribution approaches of quantities energy of the system. However, these approaches have functional effects at microscopic and macroscopic levels of that system. Therefore, this research study represents an innovative of a wi
... Show MoreDue to the importance of nanotechnology because of its features and applications in various fields, it has become the focus of attention of the world and researchers. In this study, the concept of nanotechnology and nanomaterials was identified, the most important methods of preparing them, as well as the preparation techniques and the most important devices used in their characterization.