Ethionamide structure activity relationship of imatinib

RSC Advances (v.6, #60) |

ethionamide structure activity relationship of imatinib

Ethionamide (ETH), a second-line antibiotic, is a prodrug that is activated in the BcR–Abl is an essential protein inhibited by imatinib (Gleevec™), the . The latter requires the knowledge of structure–activity relationships. minimum to rifampicin and isoniazid; figure 1), and only a quarter of these .. tuberculosis, in relation to radiographical extent of disease and amount of ( New Orleans, LA,. USA) are examining the activity of low dose imatinib damage through the loss of collagen and other structural proteins; they have. Quantitative structure-activity relationships (QSARs) vary to an appreciable extent in Stabilization of an Inactive Conformation: Imatinib, an Antileukemia Drug Isoniazid: The presently accepted mechanism of action of isoniazid proposes.

Sustained release may be achieved in multiple ways known to one ordinarily skilled in the art. Aurora kinases A and B are the most prominent. Although there are structural similarities between Aurora kinases A and B, each has a different role in both cytokinesis and tumorigenesis.

The activation of Aurora kinases is required for the optimal growth of tumor cells. Furthermore, different tumors appear to have differential sensitivity to Aurora kinase inhibitors. The amplification of Aurora kinase A is associated with highly aneuploid tumors as well as p53 dysfunction, whereas Aurora kinase B is highly associated with tumors with wild type p The impairment or ablation may be complete or partial.

Partial immunosuppression may or may not result in the inability to mount an appropriate immune response. Typically, immunocompromised refers to the depletion of a particular cell type, such as lymphocytes.

The derivative may be a prodrug. Derivatives may be prepare by any variety of synthetic methods or appropriate adaptations presented in synthetic or organic chemistry text books, such as those provide in March's Advanced Organic Chemistry: Tietze hereby incorporated by reference. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-septyl, n-octyl, n-nonyl, and the like; while saturated branched alkyls include isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, and the like.

Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1-butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methylbutenyl, 2-methylbutenyl, 2,3-dimethylbutenyl, and the like; while representative straight chain and branched alkynyls include acetylenyl, propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, 3-methylbutynyl, and the like. Representative saturated carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; while unsaturated carbocycles include cyclopentenyl and cyclohexenyl, and the like.

Heterocarbocycles include morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydroprimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, and the like.

Phenyl is a preferred aryl group. Polycyclic ring systems may, but are not required to, contain one or more non-aromatic rings, as long as one of the rings is aromatic.

Representative heteroaryls are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolinyl, isoquinolinyl, oxazolyl, isooxazolyl, benzoxazolyl, pyrazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl.

The mono- and polycyclic ring systems may be aromatic, non-aromatic or mixtures of aromatic and non-aromatic rings. Heterocycle includes heterocarbocycles, heteroaryls, and the like. An example of an alkylthio is methylthio, i. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy.

Preferred alkoxy groups are methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy. An example of an alkylamino is methylamino, i. Ra and Rb in this context may be the same or different and independently hydrogen, halogen hydroxyl, alkyl, alkoxy, alkyl, amino, alkylamino, dialkylamino, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl.

Throughout the specification, groups and substituents thereof may be chosen to provide stable moieties and compounds. The subject receiving this treatment is any animal in need, including primates, typically humans, and other mammals such as equines, cattle, swine and sheep as well as poultry and other pets.

In some embodiments, the subject has a compromised or suppressed immune system. Immunosuppression reduces the activation or efficacy of the immune system.

RSC Advances (v.6, #60)

Deliberately induced immunosuppression is typically done to prevent the body from rejecting an organ transplant e. Depending on the dose used, the mTOR described herein may result in detectable immunosuppression, via the induction of regulatory T lymphocytes by sirolimus for example Immunosuppression may be accomplished by certain agents immunosuppressants such as, but not limited to, dactinomycin, azathioprine, mycophenolic acid, leflunomide, teriflunomide, methotrexate, tacrolimus, ciclosporin, pimecrolimus, abetimus, gusperimus, lenalidomide, anakinra, sirolimus, deforolimus, everolimus, temsirolimus, zotarolimusm, biolimus A9, anti-thymocyte globulin ATGT-cell receptor directed antibodies e.

Surgery splenectomyplasmapharesis, or radiation may also cause a suppressed immune system. Since certain immunosuppressants act non-selectively, the immune system may be less able to combat tumorogenesis.

A person who is undergoing immunosuppressant therapy, or whose immune system is weak for other reasons for example, chemotherapy, HIV, and Lupus is said to be immunocompromised. Neonates are considered to immunocompromised. Certain viruses such as HIV will comprise the host immune system. In some embodiments, the disclosure relates to treating or preventing Tuberous Sclerosis by administering sirolimus and imatinib combination therapy to an immunocompromised subject.

The next day, fresh medium containing the compounds or vehicle controls was added. The Y-axis represents cell number with error bars representing the SEM. Total RNA was extracted from cell pellets pooled from two identical and independent experiments using the RNeasy mini column Qiagen.

Fluorescence intensities of each hybridized spot were determined by using the Agilent Array Scanner and the Agilent Feature Extraction Software. Two different statistical methods were used to determine differentially expressed genes: The list of differentially expressed genes in each comparison group was analyzed for statistically enriched or depleted biological classifications using the GoMiner database engine.

Equal numbers of Tsc2ang1 cells were seeded in three T flasks and treated with Vehicle control, rapamycin, imatinib or imatinib and rapamycin for 24 hours. A measure of 2. The reaction was run on the Applied Biosystems Reader for absolute quantification for well plates.

Gene expression data were automatically calculated by Sequence Detection Software, version 1. Example 4 Transcriptional Profiling Analysis RNA was extracted from tsc2ang1 cells treated with rapamycin, imatinib and a combination of the two for 24 hours. A coordinate downregulation of Aurora kinase signaling pathway was seen in cells treated with rapamycin and imatinib combination therapy FIG.

ethionamide structure activity relationship of imatinib

Western blot analysis FIG. The immunoreactive bands were visualized by enhanced chemiluminescence Amersham Biosciences. The antibodies used were: Example 5 Matrix Metalloproteinase Activity The matrix metalloproteinase MMP activity of tsc2ang1 cells treated with either imatinib or rapamycin monotherapy showed a decrease in the level of MMP-2 compared with control.

A greater reduction in the MMP bioactivity, however, was found when the cells were treated with imatinib and rapamycin in combination FIG. The presence and activity of specific MMP species were detected using gelatin zymography.

After incubation, gels were stained for 30 min in 0. FoxM1 is a transcription factor that is required for the expression of Aurora kinase B but not Aurora kinase A. This was determined by western blot analysis using a FoxM1 monoclonal antibody following cell lysis.

Two days later, intraperitoneal treatment with control, imatinib, rapamycin, and combination therapy of imatinib and rapamycin was conducted for 30 days. The compounds were suspended in 0. Thyroid nodules and goiter, thyroid enlargement, are the most common abnormalities and can be either benign or malignant processes.

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In most of these patients, circulating thyroid hormone levels are normal. Overt hyperthyroidism and hypothyroidism, thyroid hormone excess or deficiency, are usually associated with dramatic clinical manifestations. Milder disease often has a more subtle clinical presentation and is identified based on abnormal biochemical tests of thyroid function.

Screening of the newborn population for congenital hypothyroidism occurs in all developed countries, and when followed by the prompt institution of appropriate thyroid hormone replacement therapy, has dramatically decreased the incidence of mental retardation and cretinism. Maternal and neonatal hypothyroidism, due to iodine deficiency, remains the major preventable cause of mental retardation worldwide, although much progress has been made in eradicating iodine deficiency.

USA1 - Combination therapy and cancer - Google Patents

Treatment of the hypothyroid patient consists of thyroid hormone replacement. Treatment options for the hyperthyroid patient include anti-thyroid drugs to decrease hormone synthesis and secretion, destruction of the gland by the administration of radioactive iodine, or surgical removal. Encapsulation of HKNs in MBs is expected to improve the therapeutic efficacy of HK and provide a feasible technique for targeted tumor therapy.

Vertically aligned ZnO nanorods were directly grown on a seeded glass substrate between a pre-deposited source—drain to fabricate a field-effect transistor FET based ammonium ion sensor.

Controlled growth of aligned nanorods provided a well-defined large surface area for the detection of ammonium ions in solution. Theoretical study of the physisorption of organic molecules on conjugated microporous polymers: We present a computational study of the physisorption of benzene and its derivatives on a series of planar conjugated microporous polymers CMPs composed of alternative phenylene and ethynylene units, using a density-functional tight-binding method with a dispersion correction.

We focus on the significant role of the skeleton structures on the binding strength, which is one of the key factors determining both the adsorption performance and adsorption selectivity in experiments. Our calculations show that the meta-oriented phenylene moiety in the node demonstrates a stronger binding energy to organic molecules than the para-oriented phenylene unit in the linker.

Consistent with previous experimental findings, compared with CMP networks with a sole meta-oriented phenylene moiety, the existence of the para-oriented phenylene unit in the linker of the CMP frameworks will lead to smaller average binding energies to benzene derivatives. Compared to benzene, the benzene derivatives phenol, aniline, and nitrobenzene exhibit stronger physisorption.

We further find that by enlarging the size area of the linker or adding substituent groups in the node, the binding energy between the CMPs and adsorbates will increase significantly, which contributes to a better adsorption performance demonstrated in experiments. Mesoporous assembled structures of Cu2O and TiO2 nanoparticles for highly efficient photocatalytic hydrogen generation from water by I. Photocatalytic water splitting to produce hydrogen using solar energy is a particularly attractive solution to increasing energy demands.

However, to be of practical use, semiconductor electrodes need to be made of inexpensive, abundant elements and have a high, yet stable, photocatalytic H2-production activity. Here we report the first demonstration of 3D mesoporous networks of Cu2O and TiO2 nanoparticles as highly efficient photocatalysts for hydrogen generation from water.

These assembled structures feature a highly accessible pore surface that exposes a large fraction of anatase TiO2 and Cu2O nanoparticles to electrolytes, and has a small grain size of the constituent nanocrystals, which lead to excellent activity for H2 evolution via a UV-visible light-driven reduction of protons. A rare doubly nitrato and phenoxido bridged trimetallic CuII complex: In 1, in addition to the double phenoxido bridge, the two terminal CuII atoms are linked to the central CuII by means of syn—anti bridging nitrate anions giving rise to a linear arrangement.

DFT computational studies reveal that there is a clear magneto-structural correlation between the Cu—O—Cu angle and the JCu—Cu values, which is in accordance with the experimental evidence. The biological effect of 1 on the viability of different human carcinoma cells was evaluated using MTT assay and the results indicate that this complex induces a decrease in cell-population growth of human colorectal carcinoma cells COLO with apoptosis.

The synergistic effect of GNSs and LMO-MSs could significantly improve the electrical conductivity and provides more reaction sites, thereby resulting in the better electrochemical properties of the composites. The high rate capacity and longterm stability make the LMO-MSs GNSs composite a suitable electrode material for high-performance lithium-ion capacitors. Recently, two-dimensional 2D layered transition metal dichalcogenides LTMDs have attracted great scientific interest for ion battery applications.

Because of its remarkable metallic property, vanadium disulfide VS2 as a typical family member of LTMDs, can be an alternative anode material for ion battery applications. In this paper, we systematically investigate the adsorption energy and diffusion coefficient of the lithium and sodium ions in monolayer and bulk VS2 for lithium and sodium ion batteries by a density functional theory method. It exhibits a low output voltage of 0. The calculated lithium and sodium ion diffusion coefficients in the bulk VS2 are enhanced by five and seven orders of magnitude compared to the reported bulk MoS2, respectively.

Our investigations also reveal that VS2 exhibits better electrochemical performance as an anode in the sodium ion battery than in the lithium ion battery.

Synthesis of hierarchically porous carbon spheres by an emulsification-crosslinking method and their application in supercapacitors by Dingjun Zhang; Jiechang Gao; Zhangpeng Li; Shuhua He; Jinqing Wang Porous carbon materials have greatly developed as promising electrode materials for electric double-layer capacitors EDLCs. Herein, hierarchically porous carbon spheres HPCSs were synthesized by using chitosan, glutaraldehyde and KOH as the carbon source, crosslinking agent and chemical activating agent, respectively.

Moreover, the electrochemical properties characterized in a two-electrode system indicated that the specific capacitance is This paper describes the derivation of boron—manganese—carbon nanocomposites by CO2 carbonization using sodium borohydride NaBH4 as a reduction agent at 1 bar, followed by impregnation of boron-doped porous carbon BPC with a form of manganese oxide MO.

The prepared composites BPCMO can be used as an advanced electrochemical energy material, such as active electrocatalysts for oxygen reduction reaction ORR and as electrode materials for supercapacitors.

Various spectroscopic and microscopic measurements were carried out to investigate the morphology and structure of the BPCMO. It was found that impregnation of BPC with Mn3O4 enhanced electrochemical performance by generation of new active sites, increase in specific surface areas, and reduction of overall resistance.

The effect of gold nanoparticles on the diagnostic polymerase chain reaction technique for equine herpes virus 1 EHV-1 by Dalia M. Nano-biotechnology has been a noticeable research area because of its successful applications in molecular diagnostics and therapy of various genetic and microbial diseases. Although the polymerase chain reaction PCR technique is one of the most highlighted and promising applications in the molecular diagnosis field, it suffers from some drawbacks that affect its efficiency.

For instance, as a diagnostic technique for equine herpes virus-1 EHV-1conventional PCR could lead to false negative results due to the low viral titer in some samples, which leads to the necessity to improve its sensitivity. In this study, we carried out experiments to determine the effects of 15 nm unmodified citrate-coated gold nanoparticles GNPs on the key PCR reactants in order to see if these would enhance the overall outcomes of the reaction.

Our results showed that, after optimization of the GNPs, oligonucleotide primers and Taq polymerase concentrations, a specific high yield amplification with a detection limit of DNA copies could be reached compared to the to detection limit of conventional PCR.

The synthesis, characterization, removal of toxic metal ions and in vitro biological applications of a sulfanilamide—salicylic acid—formaldehyde terpolymer by V. A new terpolymer was synthesized by the polymerization of sulfanilamide, salicylic acid and formaldehyde SASF in the presence of glacial acetic acid as a catalyst.

Imatinib - DrugBank

The effect of factors affecting the metal ion adsorption on the SASF terpolymer was studied as a function of the electrolytes in different concentrations, and the influence of pH in different ranges was studied using the batch equilibrium technique.

The metal ion removal efficiency increased with an increase in the pH and concentration of the electrolytes.

ethionamide structure activity relationship of imatinib

The maximum removal percentage was achieved at pH 6—7. Inductively coupled plasma-optical emission spectroscopy ICP-OES was employed for the determination of all metal ions. The in vitro antibacterial and anticancer activities of the SASF terpolymer were also investigated.

ethionamide structure activity relationship of imatinib

The SASF terpolymer exhibited an effective antibacterial activity against Gram-positive methicillin-resistant Staphylococcus aureus, Bacillus subtilis and Gram-negative Salmonella typhi, Escherichia coli bacterial strains. The cytotoxicity studies indicated that the SASF terpolymer possesses much potential against the HeLa mammalian cancer cell line. Consequently, a series of derivatives of the found hit 1d N-[2- dimethylamino ethyl]-N- 2-phenylethyl aniline was synthesized.

To investigate the corresponding relationship between catalytic efficiency and structure, MnO2 nanomaterials nanospheres, nanosheets, nanorods have been prepared successfully, and were thoroughly characterized by SEM and TEM.

Furthermore, the selective catalytic reduction SCR performance of NOX under ammonia was used as an indicative reaction. Among the MnO2 nanomaterials with different morphologies, it was found that their SCR activities showed an interesting variation tendency: It is found that surface chemisorbed oxygen, specific surface area, reducibility and acid sites have great influence on the NO removal efficiency in the SCR reaction.

Endothelial cell mediated inflammation flags and mediates the progression of pre and post myocardial infarction. NCCL reduced endothelial cell mediated inflammation by reducing endothelial microparticle generation.

ethionamide structure activity relationship of imatinib

Hybrid composite materials are particularly useful and offer great opportunities for catalysis due to their multifunctionalities. The introduction of single-layer MoS2 nanosheets not only improves porous PtCu nanoparticles with a fine dispersion, but also readily incorporates recognition elements.

Microwave-assisted single-surfactant templating synthesis of mesoporous zeolites by Maria J. Costa; Jowita Marszewska; Alexandre A.

ethionamide structure activity relationship of imatinib

Araujo; Mietek Jaroniec A single-surfactant templating method was explored for the synthesis of mesoporous zeolites under microwave irradiation, which allowed programming of temperature and time over a wide range of conditions and resulted in a significant reduction of the synthesis time.

Most importantly, this approach eliminated the use of an organic molecular template for creating microporous zeolitic structure. Two preparation methods were examined: Mesopores were created by soft-templating, whereas the crystalline microporous framework was formed in the absence of organic molecular template under microwave irradiation.

One of the samples was tested as a catalyst in the cracking of vacuum gas oil, which resulted in obtaining hydrocarbons in the range of liquefied petroleum gas, gasoline and diesel, indicating that the mesoporous zeolitic materials prepared via single-surfactant templating under microwave irradiation are effective catalysts for the pyrolysis of vacuum gas oil.

Both the synthesis procedure and the presented application of mesoporous zeolites address a few aspects of green chemistry and sustainability.